Skip to main content
SpringerLink
Log in

Connexins in Growth Control and Cancer

  • Chapter
Book cover Gap Junctions in Development and Disease

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ai Z, Fischer A, Spray DC, Brown AM, Fishman GI (2000) Wnt-1 regulation of connexin43 in cardiac myocytes. J Clin Invest 105:161–171

    PubMed  Google Scholar 

  • Alexander DB, Goldberg GS (2003) Transfer of biologically important molecules between cells through gap junction channels. Curr Med Chem 10:2045–2058

    Article  PubMed  Google Scholar 

  • Alexander DB, Ichikawa H, Bechberger JF, Valiunas V, Ohki M, Naus CC, Kunimoto T, Tsuda H, Miller WT, Goldberg GS (2004) Normal cells control the growth of neighboring transformed cells independent of gap junctional communication and SRC activity. Cancer Res 64:1347–1358

    Article  PubMed  Google Scholar 

  • Andrade-Rozental AF, Rozental R, Hopperstad MG, Wu JK, Vrionis FD, Spray DC (2000) Gap junctions: the “kiss of death” and the “kiss of life”. Brain Res Brain Res Rev 32:308–315

    Article  PubMed  Google Scholar 

  • Azarnia R, Mitcho M, Shalloway D, Loewenstein WR (1989) Junctional intercellular communication is cooperatively inhibited by oncogenes in transformation. Oncogene 4:1161–1168

    PubMed  Google Scholar 

  • Azzam EI, de Toledo SM, Gooding T, Little JB (1998) Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles. Radiat Res 150:497–504

    PubMed  Google Scholar 

  • Azzam EI, de Toledo SM, Little JB (2003) Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect. Oncogene 22:7050–7057

    Article  PubMed  Google Scholar 

  • Bani-Yaghoub M, Felker JM, Sans C, Naus CC (2000) The effects of bone morphogenetic protein 2 and 4 (BMP2 and BMP4) on gap junctions during neurodevelopment. Exp Neurol 162:13–26

    Article  PubMed  Google Scholar 

  • Bignami M, Rosa S, Falcone G, Tato F, Katoh F, Yamasaki H (1988) Specific viral oncogenes cause differential effects on cell-to-cell communication, relevant to the suppression of the transformed phenotype by normal cells. Mol Carcinog 1:67–75

    PubMed  Google Scholar 

  • Bowling N, Huang X, Sandusky GE, Fouts RL, Mintze K, Esterman M, Allen PD, Maddi R, McCall E, Vlahos CJ (2001) Protein kinase C-alpha and-epsilon modulate connexin-43 phosphorylation in human heart. J Mol Cell Cardiol 33:789–798

    Article  PubMed  Google Scholar 

  • Brigstock DR (2003) The CCN family: a new stimulus package. J Endocrinol 178:169–175

    Article  PubMed  Google Scholar 

  • Butkevich E, Hulsmann S, Wenzel D, Shirao T, Duden R, Majoul I (2004) Drebrin is a novel connexin-43 binding partner that links gap junctions to the submembrane cytoskeleton. Curr Biol 14:650–658

    Article  PubMed  Google Scholar 

  • Carystinos GD, Katabi MM, Laird DW, Galipeau J, Chan H, Alaoui-Jamali MA, Batist G (1999) Cyclic-AMP induction of gap junctional intercellular communication increases bystander effect in suicide gene therapy. Clin Cancer Res 5:61–68

    PubMed  Google Scholar 

  • Chatterjee B, Meyer RA, Loredo GA, Coleman CM, Tuan R, Lo CW (2003) BMP regulation of the mouse connexin43 promoter in osteoblastic cells and embryos. Cell Commun Adhes 10:37–50

    Article  PubMed  Google Scholar 

  • Chaumontet C, Droumaguet C, Bex V, Heberden C, Gaillard-Sanchez I, Martel P (1997) Flavonoids (apigenin, tangeretin) counteract tumor promoter-induced inhibition of intercellular communication of rat liver epithelial cells. Cancer Lett 114: 207–210

    Article  PubMed  Google Scholar 

  • Chen SC, Pelletier DB, Ao P, Boynton AL (1995) Connexin43 reverses the phenotype of transformed cells and alters their expression of cyclin/cyclin-dependent kinases. Cell Growth Differ 6:681–690

    PubMed  Google Scholar 

  • Contreras JE, Sanchez HA, Eugenin EA, Speidel D, Theis M, Willecke K, Bukauskas FF, Bennett MV, Saez JC (2002) Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc Natl Acad Sci USA 99:495–500

    Article  PubMed  Google Scholar 

  • Cooper CD, Lampe PD (2002) Casein kinase 1 regulates connexin-43 gap junction assembly. J Biol Chem 277:44962–44968

    Article  PubMed  Google Scholar 

  • Cruciani V, Mikalsen SO (2002) Connexins, gap junctional intercellular communication and kinases. Biol Cell 94:433–443

    Article  PubMed  Google Scholar 

  • Dang X, Doble BW, Kardami E (2003) The carboxy-tail of connexin-43 localizes to the nucleus and inhibits cell growth. Mol Cell Biochem 242:35–38

    Article  PubMed  Google Scholar 

  • Das PM, Singal R (2004) DNA methylation and cancer. J Clin Oncol 22:4632–4642

    Article  PubMed  Google Scholar 

  • De Maio A, Vega VL, Contreras JE (2002) Gap junctions, homeostasis, and injury. J Cell Physiol 191:269–282

    Article  PubMed  Google Scholar 

  • Defeijter AW, Matesic DF, Ruch RJ, Guan XJ, Chang CC, Trosko JE (1996) Localization and function of the connexin 43 gap-junction protein in normal and various oncogene-expressing rat liver epithelial cells. Mol Carcinogenesis 16:203–212

    Article  Google Scholar 

  • Dermietzel R, Meier C, Bukauskas F, Spray DC (2003) Following tracks of hemichannels. Cell Commun Adhes 10:335–340

    PubMed  Google Scholar 

  • Deschenes SM, Walcott JL, Wexler TL, Scherer SS, Fischbeck KH (1997) Altered trafficking of mutant connexin32. J Neurosci 17:9077–9084

    PubMed  Google Scholar 

  • Dilber M, Abedi MR, Christensson B, Bjorkstrand B, Kidder GM, Naus CCG, Gahrton G, Smith CIE (1997) Gap junctions promote the bystander effect of Herpes Simplex thymidine kinase in vivo. Cancer Res 57:1523–1528

    PubMed  Google Scholar 

  • Ding HF, Fisher DE (2002) Induction of apoptosis in cancer: new therapeutic opportunities. Ann Med 34:451–469

    Article  PubMed  Google Scholar 

  • Doble BW, Ping P, Kardami E (2000) The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation. Circ Res 86:293–301

    PubMed  Google Scholar 

  • Dubina MV, Iatckii NA, Popov DE, Vasil’ev SV, Krutovskikh VA (2002) Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Oncogene 21:4992–4996

    Article  PubMed  Google Scholar 

  • Duffy HS, Delmar M, Spray DC (2002) Formation of the gap junction nexus: binding partners for connexins. J Physiol Paris 96:243–249

    Article  PubMed  Google Scholar 

  • Ebihara L (2003) New roles for connexons. News Physiol Sci 18:100–103

    PubMed  Google Scholar 

  • Echetebu CO, Ali M, Izban MG, MacKay L, Garfield RE (1999) Localization of regulatory protein binding sites in the proximal region of human myometrial connexin 43 gene. Mol Hum Reprod 5:757–766

    Article  PubMed  Google Scholar 

  • Eghbali B, Kessler JA, Reid LM, Roy C, Spray DC (1991) Involvement of gap junctions in tumorigenesis: transfection of tumor cells with connexin 32 cDNA retards growth in vivo. Proc Natl Acad Sci USA 88:10701–10705

    PubMed  Google Scholar 

  • Enomoto T, Sasaki Y, Shiba Y, Kanno Y, Yamasaki H (1981) Tumor promoters cause a rapid and reversible inhibition of the formation and maintenance of electrical cell coupling in culture. Proc Natl Acad Sci USA 78:5628–5632

    PubMed  Google Scholar 

  • Esinduy CB, Chang CC, Trosko JE, Ruch RJ (1995) In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: Requirement for gap junctional intercellular communication. Carcinogenesis 16:915–921

    PubMed  Google Scholar 

  • Fu CT, Bechberger JF, Ozog MA, Perbal B, Naus CC (2004) CCN3 (NOV) Interacts with Connexin43 in C6 Glioma Cells: Possible mechanism of connexin-mediated growth suppression. J Biol Chem 279:36943–36950

    Article  PubMed  Google Scholar 

  • Gellhaus A, Dong X, Propson S, Maass K, Klein-Hitpass L, Kibschull M, Traub O, Willecke K, Perbal B, Lye SJ, Winterhager E (2004) Connexin43 interacts with NOV: A possible mechanism for negative regulation of cell growth in choriocarcinoma cells. J Biol Chem 279:36931–36942

    Article  PubMed  Google Scholar 

  • Giepmans BN, Moolenaar WH (1998) The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein. Curr Biol 8:931–934

    Article  PubMed  Google Scholar 

  • Giepmans BN, Hengeveld T, Postma FR, Moolenaar WH (2001a) Interaction of c-Src with gap junction protein connexin-43. Role in the regulation of cell-cell communication. J Biol Chem 276:8544–8549

    Article  PubMed  Google Scholar 

  • Giepmans BN, Verlaan I, Hengeveld T, Janssen H, Calafat J, Falk MM, Moolenaar WH (2001b) Gap junction protein connexin-43 interacts directly with microtubules. Curr Biol 11:1364–1368

    Article  PubMed  Google Scholar 

  • Goldberg GS, Martyn KD, Lau AF (1994) A connexin 43 antisense vector reduces the ability of normal cells to inhibit the foci formation of transformed cells. Mol Carcinogen 11:106–114

    Google Scholar 

  • Goldberg GS, Lampe PD, Sheedy D, Stewart CC, Nicholson BJ, Naus CCG (1998) Direct isolation and analysis of endogenous transjunctional ADP from Cx43 transfected C6 glioma cells. Exp Cell Res 239:82–92

    Article  PubMed  Google Scholar 

  • Goldberg GS, Lampe PD, Nicholson BJ (1999) Selective transfer of endogenous metabolites through gap junctions composed of different connexins. Nat Cell Biol 1:457–459

    Article  PubMed  Google Scholar 

  • Goldberg GS, Bechberger JF, Tajima Y, Merritt M, Omori Y, Gawinowicz MA, Narayanan R, Tan Y, Sanai Y, Yamasaki H, Naus CC, Tsuda H, Nicholson BJ (2000) Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells. Cancer Res 60:6018–6026

    PubMed  Google Scholar 

  • Goldberg GS, Moreno AP, Lampe PD (2002) Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP. J Biol Chem 277:36725–36730

    Article  PubMed  Google Scholar 

  • Govindarajan R, Zhao S, Song XH, Guo RJ, Wheelock M, Johnson KR, Mehta PP (2002) Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by alpha-catenin. J Biol Chem 277:50087–50097

    Article  PubMed  Google Scholar 

  • Gupta N, Wang H, Mcleod TL, Naus CCG, Kyurkchiev S, Advani S, Yu J, Perbal B, Weichselbaum RR (2001) Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV). J Clin Path Mol Path 54:293–299

    Google Scholar 

  • Hayashi T, Nomata K, Chang CC, Ruch RJ, Trosko JE (1998) Cooperative effects of v-myc and c-Ha-ras oncogenes on gap junctional intercellular communication and tumorigenicity in rat liver epithelial cells. Cancer Lett 128:145–154

    Article  PubMed  Google Scholar 

  • Herve JC, Sarrouilhe D (2002) Modulation of junctional communication by phosphorylation: protein phosphatases, the missing link in the chain. Biol Cell 94:423–432

    Article  PubMed  Google Scholar 

  • Herve JC, Bourmeyster N, Sarrouilhe D (2004) Diversity in protein-protein interactions of connexins: emerging roles. Biochim Biophys Acta 1662:22–41

    PubMed  Google Scholar 

  • Hirai A, Yano T, Nishikawa K, Suzuki K, Asano R, Satoh H, Hagiwara K, Yamasaki H (2003) Down-regulation of connexin 32 gene expression through DNA methylation in a human renal cell carcinoma cell. Am J Nephrol 23:172–177

    Article  PubMed  Google Scholar 

  • Hossain MZ, Bertram JS (1994) Retinoids suppress proliferation, induce cell spreading, and up-regulate connexin43 expression only in postconfluent 10T1/2 cells: Implications for the role of gap junctional communication. Cell Growth Differ 5:1253–1261

    PubMed  Google Scholar 

  • Huang RP, Fan Y, Hossain MZ, Peng A, Zeng ZL, Boynton AL (1998) Reversion of the neoplastic phenotype of human glioblastoma cells by connexin 43 (cx43). Cancer Res 58:5089–5096

    PubMed  Google Scholar 

  • Huang R, Liu YG, Lin Y, Fan Y, Boynton A, Yang D, Huang RP (2001a) Enhanced apoptosis under low serum conditions in human glioblastoma cells by connexin 43 (Cx43). Mol Carcinogenesis 32:128–138

    Article  Google Scholar 

  • Huang RP, Hossain MZ, Huang R, Gano J, Fan Y, Boynton AL (2001b) Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells. Int J Cancer 92:130–138

    Article  PubMed  Google Scholar 

  • Jensen R, Glazer PM (2004) Cell-interdependent cisplatin killing by Ku/DNA-dependent protein kinase signaling transduced through gap junctions. Proc Natl Acad Sci USA 101:6134–6139

    Article  PubMed  Google Scholar 

  • Joliot V, Martinerie C, Dambrine G, Plassiart G, Brisac M, Crochet J, Perbal B (1992) Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. Mol Cell Biol 12:10–21

    PubMed  Google Scholar 

  • Jou YS, Layhe B, Matesic DF, Chang CC, Defeijter AW, Lockwood L, Welsch CW, Klaunig JE, Trosko JE (1995) Inhibition of gap junctional intercellular communication and malignant transformation of rat liver epithelial cells by neu oncogene. Carcinogenesis 16:311–317

    PubMed  Google Scholar 

  • Kalimi GH, Hampton LL, Trosko JE, Thorgeirsson SS, Huggett AC (1992) Homologous and heterologous gap-junctional intercellular communication in v-raf-, v-myc-, and v-raf/v-myc-transduced rat liver epithelial cell lines. Mol Carcinogenesis 5:301–310

    Google Scholar 

  • Kanemitsu MY, Loo LWM, Simon S, Lau AF, Eckhart W (1997) Tyrosine phosphorylation of connexin 43 by v-SRC is mediated by SH2 and SH3 domain interactions. J Biol Chem 272:22824–22831

    Article  PubMed  Google Scholar 

  • Kapoor P, Saunders MM, Li Z, Zhou Z, Sheaffer N, Kunze EL, Samant RS, Welch DR, Donahue HJ (2004) Breast cancer metastatic potential: correlation with increased heterotypic gap junctional intercellular communication between breast cancer cells and osteoblastic cells. Int J Cancer 111:693–697

    Article  PubMed  Google Scholar 

  • King TJ, Lampe PD (2004a) Mice deficient for the gap junction protein Connexin32 exhibit increased radiation-induced tumorigenesis associated with elevated mitogen-activated protein kinase (p44/Erk1, p42/Erk2) activation. Carcinogenesis 25:669–680

    Article  PubMed  Google Scholar 

  • King TJ, Lampe PD (2004b) The gap junction protein connexin32 is a mouse lung tumor suppressor. Cancer Res 64:7191–7196

    Article  PubMed  Google Scholar 

  • King TJ, Fukushima LH, Donlon TA, Hieber AD, Shimabukuro KA, Bertram JS (2000) Correlation between growth control, neoplastic potential and endogenous connexin43 expression in HeLa cell lines: implications for tumor progression. Carcinogenesis 21:311–315

    Article  PubMed  Google Scholar 

  • Laing JG, Tadros PN, Westphale EM, Beyer EC (1997) Degradation of connexin43 gap junctions involves both the proteasome and the lysosome. Exp Cell Res 236:482–492

    Article  PubMed  Google Scholar 

  • Lampe PD (1994) Analyzing phorbol ester effects on gap junctional communication: A dramatic inhibition of assembly. J Cell Biol 127:1895–1905

    Article  PubMed  Google Scholar 

  • Lampe PD, Lau AF (2000) Regulation of gap junctions by phosphorylation of connexins. Arch Biochem Biophys 384:205–215

    Article  PubMed  Google Scholar 

  • Lampe PD, Lau AF (2004) The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol 36:1171–1186

    Article  PubMed  Google Scholar 

  • Lampe PD, Tenbroek EM, Burt JM, Kurata WE, Johnson RG, Lau AF (2000) Phosphorylation of connexin43 onserine368 by protein kinase C regulates gap junctional communication. J Cell Biol 149:1503–1512

    Article  PubMed  Google Scholar 

  • Leithe E, Rivedal E (2004) Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43. J Cell Sci 117:1211–1220

    Article  PubMed  Google Scholar 

  • Lin C, Weigel H, Cotrina ML, Liu S, Bueno E, Hansen AJ, Hansen TW, Goldman S, Nedergaard M (1998) Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci 1:494–500

    Article  PubMed  Google Scholar 

  • Lin JH, Yang J, Liu S, Takano T, Wang X, Gao Q, Willecke K, Nedergaard M (2003) Connexin mediates gap junction-independent resistance to cellular injury. J Neurosci 23:430–441

    PubMed  Google Scholar 

  • Loewenstein WR, Kanno Y (1966) Intercellular communication and the control of tissue growth: lack of communication between cancer cells. Nature 209:1248–1249

    PubMed  Google Scholar 

  • Loncarek J, Yamasaki H, Levillain P, Milinkevitch S, Mesnil M (2003) The expression of the tumor suppressor gene connexin 26 is not mediated by methylation in human esophageal cancer cells. Mol Carcinogenesis 36:74–81

    Article  Google Scholar 

  • Mcleod TL, Bechberger JF, Naus CC (2001) Determination of a potential role of the CCN family of growth regulators in connexin43 transfected C6 glioma cells. Cell Commun Adhes 8:441–445

    PubMed  Google Scholar 

  • Mehta PP, Bertram JS, Loewenstein WR (1986) Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44:187–196

    Article  PubMed  Google Scholar 

  • Mehta PP, Bertram JS, Loewenstein WR (1989) The actions of retinoids on cellular growth correlate with their actions on gap junctional communication. J Cell Biol 108:1053–1065

    Article  PubMed  Google Scholar 

  • Mehta PP, Hotz-Wagenblatt A, Rose B, Shalloway D (1991) Incorporation of the gene for a cell-cell channel protein into transformed cells leads to normalization of growth. J Membr Biol 124:207–225

    Article  PubMed  Google Scholar 

  • Mesnil M (2002) Connexins and cancer. Biol Cell 94:493–500

    Article  PubMed  Google Scholar 

  • Mesnil M, Krutovskikh V, Piccoli C, Elfgang C, Traub O, Willecke K, Yamasaki H (1995) Negative growth control of HeLa cells by connexin genes: Connexin species specificity. Cancer Res 55:629–639

    PubMed  Google Scholar 

  • Mesnil M, Piccoli C, Tiraby G, Willecke K, Yamasaki H (1996) Bystander killing of cancer cells by HSV-TK gene is mediated by connexins. Proc Natl Acad Sci USA 93:1831–1835

    Article  PubMed  Google Scholar 

  • Moorby C, Patel M (2001) Dual functions for connexins: Cx43 regulates growth independently of gap junction formation. Exp Cell Res 271:238–248

    Article  PubMed  Google Scholar 

  • Musil LS, Goodenough DA (1991)Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. J Cell Biol 115:1357–1374

    Article  PubMed  Google Scholar 

  • Musil LS, Le AC, VanSlyke JK, Roberts LM (2000) Regulation of connexin degradation as a mechanism to increase gap junction assembly and function. J Biol Chem 275:25207–25215

    Article  PubMed  Google Scholar 

  • Mussini I, Biral D, Marin O, Furlan S, Salvatori S (1999) Myotonic dystrophy protein kinase expressed in rat cardiac muscle is associated with sarcoplasmic reticulum and gap junctions. J Histochem Cytochem 47:383–392

    PubMed  Google Scholar 

  • Nagafuchi A (2001) Molecular architecture of adherens junctions. Curr Opin Cell Biol 13:600–603

    Article  PubMed  Google Scholar 

  • Naus CC, Bond SL, Bechberger JF, Rushlow W (2000) Identification of genes differentially expressed in C6 glioma cells transfected with connexin43. Brain Res Brain Res Rev 32:259–266

    Article  PubMed  Google Scholar 

  • Nicholas TW, Read SB, Burrows FJ, Kruse CA (2003) Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects. Histol Histopathol 18:495–507

    PubMed  Google Scholar 

  • Nishimura M, Saito T, Yamasaki H, Kudo R (2003) Suppression of gap junctional intercellular communication via 5′ CpG island methylation in promoter region of E-cadherin gene in endometrial cancer cells. Carcinogenesis 24:1615–1623

    Article  PubMed  Google Scholar 

  • Olbina G, Eckhart W (2003) Mutations in the second extracellular region of connexin 43 prevent localization to the plasma membrane, but do not affect its ability to suppress cell growth. Mol Cancer Res 1:690–700

    PubMed  Google Scholar 

  • Ozog MA, Bechberger JF, Naus CC (2002) Ciliary neurotrophic factor (CNTF) in combination with its soluble receptor (CNTFRα) increases connexin43 expression and suppresses growth of C6 glioma cells. Cancer Res 62:3544–3548

    PubMed  Google Scholar 

  • Ozog MA, Bernier SM, Bates DC, Chatterjee B, Lo CW, Naus CC (2004) The complex of CNTF-CNTFRα upregulates connexin43 and intercellular coupling in astrocytes via the JAK/STAT pathway. Mol Biol Cell (in press)

    Google Scholar 

  • Peracchia C, Sotkis A, Wang XG, Peracchia LL, Persechini A (2000) Calmodulin directly gates gap junction channels. J Biol Chem 275:26220–26224

    Article  PubMed  Google Scholar 

  • Perbal B (2001) NOV (nephroblastoma overexpressed) and the CCN family of genes: structural and functional issues. Mol Pathol 54:57–79

    Article  PubMed  Google Scholar 

  • Perbal B (2004) CCN proteins: multifunctional signalling regulators. Lancet 363:62–64

    Article  PubMed  Google Scholar 

  • Piechocki MP, Burk RD, Ruch RJ (1999) Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. Carcinogenesis 20:401–406

    Article  PubMed  Google Scholar 

  • Planque N, Perbal B (2003) A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis. Cancer Cell Int 3:15

    Article  PubMed  Google Scholar 

  • Princen F, Robe P, Gros D, Jarry-Guichard T, Gielen J, Merville MP, Bours V (2001) Rat gap junction connexin-30 inhibits proliferation of glioma cell lines. Carcinogenesis 22:507–513

    Article  PubMed  Google Scholar 

  • Qin H, Shao Q, Thomas T, Kalra J, Alaoui-Jamali MA, Laird DW (2003) Connexin26 regulates the expression of angiogenesis-related genes in human breast tumor cells by both GJIC-dependent and-independent mechanisms. Cell Commun Adhes 10:387–393

    PubMed  Google Scholar 

  • Reuss B, Unsicker K (1998) Regulation of gap junction communication by growth factors from non-neural cells to astroglia — a brief review. GLIA 24:32–38

    Article  PubMed  Google Scholar 

  • Robe PA, Princen F, Martin D, Malgrange B, Stevenaert A, Moonen G, Gielen J, Merville M, Bours V (2000) Pharmacological modulation of the bystander effect in the herpes simplex virus thymidine kinase/ganciclovir gene therapy system: effects of dibutyryl adenosine 3′,′-cyclic monophosphate, alpha-glycyrrhetinic acid, and cytosine arabinoside. Biochem Pharmacol 60:241–249

    Article  PubMed  Google Scholar 

  • Robe PA, Jolois O, N’Guyen M, Princen F, Malgrange B, Merville MP, Bours V (2004) Modulation of the HSV-TK/ganciclovir bystander effect by n-butyrate in glioblastoma: correlation with gap-junction intercellular communication. Int J Oncol 25:187–192

    PubMed  Google Scholar 

  • Rose B, Mehta PP, Loewenstein WR (1993) Gap-junction protein gene suppresses tumorigenicity. Carcinogenesis 14:1073–1075

    PubMed  Google Scholar 

  • Samejima Y, Meruelo D (1995) ’Bystander killing’ induces apoptosis and is inhibited by forskolin. Gene Therapy 2:50–58

    PubMed  Google Scholar 

  • Saunders MM, Seraj MJ, Li Z, Zhou Z, Winter CR, Welch DR, Donahue HJ (2001) Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication. Cancer Res 61:1765–1767

    PubMed  Google Scholar 

  • Schiavon G, Furlan S, Marin O, Salvatori S (2002) Myotonic dystrophy protein kinase of the cardiac muscle: evaluation using an immunochemical approach. Microsc Res Tech 58:404–411

    Article  PubMed  Google Scholar 

  • Segretain D, Decrouy X, Dompierre J, Escalier D, Rahman N, Fiorini C, Mograbi B, Siffroi JP, Huhtaniemi I, Fenichel P, Pointis G (2003) Sequestration of connexin43 in the early endosomes: an early event of Leydig cell tumor progression. Mol Carcinogenesis 38:179–187

    Article  Google Scholar 

  • Seul KH, Kang KY, Lee KS, Kim SH, Beyer EC (2004) Adenoviral delivery of human connexin37 induces endothelial cell death through apoptosis. Biochem Biophys Res Commun 319:1144–1151

    Article  PubMed  Google Scholar 

  • Shevde LA, Samant RS, Goldberg SF, Sikaneta T, Alessandrini A, Donahue HJ, Mauger DT, Welch DR (2002) Suppression of human melanoma metastasis by the metastasis suppressor gene, BRMS1. Exp Cell Res 273:229–239

    Article  PubMed  Google Scholar 

  • Simon AM, Goodenough DA (1998) Diverse functions of vertebrate gap junctions. Trends Cell Biol 8:477–483

    Article  PubMed  Google Scholar 

  • Singal R, Tu ZJ, Vanwert JM, Ginder GD, Kiang DT (2000) Modulation of the connexin26 tumor suppressor gene expression through methylation in human mammary epithelial cell lines. Anticancer Res 20:59–64

    PubMed  Google Scholar 

  • Sohl G, Willecke K (2004) Gap junctions and the connexin protein family. Cardiovasc Res 62:228–232

    Article  PubMed  Google Scholar 

  • Stoker MG, Shearer M, O’Neill C (1966) Growth inhibition of polyoma-transformed cells by contact with static normal fibroblasts. J Cell Sci 1:297–310

    PubMed  Google Scholar 

  • Stout CE, Costantin JL, Naus CC, Charles AC (2002) Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem 277:10482–10488

    Article  PubMed  Google Scholar 

  • Swierenga SH, Yamasaki H (1992) Performance of tests for cell transformation and gap-junction intercellular communication for detecting nongenotoxic carcinogenic activity. IARC Sci Publ 165–193

    Google Scholar 

  • Tan LW, Bianco T, Dobrovic A (2002) Variable promoter region CpG island methylation of the putative tumor suppressor gene connexin 26 in breast cancer. Carcinogenesis 23:231–236

    Article  PubMed  Google Scholar 

  • Temme A, Buchmann A, Gabriel HD, Nelles E, Schwarz M, Willecke K (1997) High incidence of spontaneous and chemically induced liver tumors in mice deficient for connexin32. Curr Biol 7:713–716

    Article  PubMed  Google Scholar 

  • Teunissen BE, Jansen AT, van Amersfoorth SC, O’Brien TX, Jongsma HJ, Bierhuizen MF (2003) Analysis of the rat connexin 43 proximal promoter in neonatal cardiomyocytes. Gene 322:123–136

    Article  PubMed  Google Scholar 

  • Thomas T, Aasen T, Hodgins M, Laird DW (2003) Transport and function of cx26 mutants involved in skin and deafness disorders. Cell Commun Adhes 10:353–358

    PubMed  Google Scholar 

  • Torok K, Stauffer K, Evans WH (1997) Connexin32 of gap junctions contains two cytoplasmic calmodulin-binding domains. Biochem J 326:479–483

    PubMed  Google Scholar 

  • Touraine RL, Vahanian N, Ramsey WJ, Blaese RM (1998) Enhancement of the herpes simplex virus thymidine kinase/ganciclovir bystander effect and its antitumor efficacy in vivo by pharmacologic manipulation of gap junctions. Hum Gene Therapy 9:2385–2391

    Google Scholar 

  • Toyofuku T, Akamatsu Y, Zhang H, Kuzuya T, Tada M, Hori M (2001) c-Src regulates the interaction between connexin-43 and ZO-1 in cardiac myocytes. J Biol Chem 276:1780–1788

    Article  PubMed  Google Scholar 

  • Trosko JE, Goodman JI (1994) Intercellular communication may facilitate apoptosis: Implications for tumor promotion. Mol Carcinogenesis 11:8–12

    Google Scholar 

  • Trosko JE, Chang CC (2001) Mechanism of up-regulated gap junctional intercellular communication during chemoprevention and chemotherapy of cancer. Mutat Res 480–481:219–229

    PubMed  Google Scholar 

  • Trosko JE, Ruch RJ (2002) Gap junctions as targets for cancer chemoprevention and chemotherapy. Curr Drug Targets 3:465–482

    Article  PubMed  Google Scholar 

  • van der Heyden MA, Rook MB, Hermans MM, Rijksen G, Boonstra J, Defize LH, Destree OH (1998) Identification of connexin43 as a functional target for Wnt signalling. J Cell Sci 111:1741–1749

    PubMed  Google Scholar 

  • Van Eldik LJ, Hertzberg EL, Berdan RC, Gilula NB (1985) Interaction of calmodulin and other calcium-modulated proteins with mammalian and arthropod junctional membrane proteins. Biochem Biophys Res Commun 126:825–832

    Article  PubMed  Google Scholar 

  • Vine AL, Bertram JS (2002) Cancer chemoprevention by connexins. Cancer Metastasis Rev 21:199–216

    Article  PubMed  Google Scholar 

  • Warn-Cramer BJ, Lau AF (2004) Regulation of gap junctions by tyrosine protein kinases. Biochim Biophys Acta 1662:81–95

    PubMed  Google Scholar 

  • Warn-Cramer BJ, Lin R, Martyn K, Guyette CV, Lau AF (2003) Maintaining connexin43 gap junctional communication in v-Src cells does not alter growth properties associated with the transformed phenotype. Cell Commun Adhes 10:299–303

    PubMed  Google Scholar 

  • Xu X, Li WE, Huang GY, Meyer R, Chen T, Luo Y, Thomas MP, Radice GL, Lo CW (2001) Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions. J Cell Biol 154:217–230

    Article  PubMed  Google Scholar 

  • Yamasaki H, Naus CCG (1996) Role of connexin genes in growth control. Carcinogenesis 17:1199–1213

    PubMed  Google Scholar 

  • Yano T, Ito F, Kobayashi K, Yonezawa Y, Suzuki K, Asano R, Hagiwara K, Nakazawa H, Toma H, Yamasaki H (2004) Hypermethylation of the CpG island of connexin 32, a candidate tumor suppressor gene in renal cell carcinomas from hemodialysis patients. Cancer Lett 208:137–142

    Article  PubMed  Google Scholar 

  • Yu W, Dahl G, Werner R (1994) The connexin43 gene is responsive to oestrogen. Proc R Soc Lond [Biol] 255:125–132

    Google Scholar 

  • Zhang YW, Kaneda M, Morita I (2003) The gap junction-independent tumor-suppressing effect of connexin 43. J Biol Chem 278:44852–44856

    Article  PubMed  Google Scholar 

  • Zhang ZQ, Zhang W, Wang NQ, Bani-Yaghoub M, Lin ZX, Naus CC (1998) Suppression of tumorigenicity of human lung carcinoma cells after transfection with connexin43. Carcinogenesis 19:1889–1894

    Article  PubMed  Google Scholar 

  • Zhou L, Kasperek EM, Nicholson BJ (1999) Dissection of the molecular basis of pp60(v-src) induced gating of connexin 43 gap junction channels. J Cell Biol 144:1033–1045

    Article  PubMed  Google Scholar 

  • Zhu D, Caveney S, Kidder GM, Naus CC (1991) Transfection of C6 glioma cells with connexin 43 cDNA: analysis of expression, intercellular coupling, and cell proliferation. Proc Natl Acad Sci USA 88:1883–1887

    PubMed  Google Scholar 

  • Zhu D, Kidder GM, Caveney S, Naus CC (1992)Growth retardation in glioma cells cocultured with cells overexpressing a gap junction protein. Proc Natl Acad Sci USA 89:10218–10221

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada

    Christian C. Naus & Wun Chey Sin

  2. Department of Molecular Biology, University of Medicine and Dentistry of New Jersey, Stratford, NJ, 08084

    Gary S. Goldberg

Authors
  1. Christian C. Naus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gary S. Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wun Chey Sin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical Faculty of the University Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Elke Winterhager

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Naus, C.C., Goldberg, G.S., Sin, W.C. (2005). Connexins in Growth Control and Cancer. In: Winterhager, E. (eds) Gap Junctions in Development and Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-28621-7_12

Download citation

Publish with us

Policies and ethics

Search

Navigation