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Abrogation of Transforming Growth Factor-β Signaling in Pancreatic Cancer

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Abstract

Transforming growth factor-β (TGFβ) functions as a growth inhibitor for many cell types by inhibiting cell cycle progression. Loss of TGFβ responsiveness can lead to deregulated cell proliferation and ultimately tumor progression. For example, the TGFβ signaling pathway is a frequent target for inactivation in pancreatic cancer. Functional connection between the potent growth inhibitory activity of TGFβ and the tumor suppressor activity of Smads has been well documented. Smads directly modulate transcription of the genes involved in cell cycle progression in response to TGFβ, and that abrogation of this regulation leads to tumor progression. In this review, we summarize recent research progress on TGFβ signaling and pancreatic cancer.

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References

  1. D Hanahan RA Weinberg (2000) ArticleTitleThe hallmarks of cancer Cell 100 57–70 Occurrence Handle1:CAS:528:DC%2BD3cXks1CktA%3D%3D Occurrence Handle10647931

    CAS  PubMed  Google Scholar 

  2. J Hoeijmakers (2001) ArticleTitleGenome maintenance mechanisms for preventing cancer Nature 411 366–374 Occurrence Handle10.1038/35077232 Occurrence Handle1:CAS:528:DC%2BD3MXktVSjs74%3D Occurrence Handle11357144

    Article  CAS  PubMed  Google Scholar 

  3. A Balmain J Gray B Ponder (2003) ArticleTitleThe genetics and genomics of cancer Nat. Genet. 33 IssueIDSupp.l 238–244 Occurrence Handle10.1038/ng1107 Occurrence Handle1:CAS:528:DC%2BD3sXhsV2kt7c%3D Occurrence Handle12610533

    Article  CAS  PubMed  Google Scholar 

  4. G Evan K Vousden (2001) ArticleTitleProliferation, cell cycle and apoptosis in cancer Nature 411 342–348 Occurrence Handle1:CAS:528:DC%2BD3MXktVSjsr8%3D Occurrence Handle11357141

    CAS  PubMed  Google Scholar 

  5. P Brume-Jensen T Hunter (2001) ArticleTitleOncogenic kinase signaling Nature 411 355–365 Occurrence Handle10.1038/35077225 Occurrence Handle11357143

    Article  PubMed  Google Scholar 

  6. BJ Druker S Tamura E Buchdunger et al. (1996) ArticleTitleEffects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells Nat. Med. 2 561–566 Occurrence Handle10.1038/nm0596-561 Occurrence Handle1:CAS:528:DyaK28Xislyhs70%3D Occurrence Handle8616716

    Article  CAS  PubMed  Google Scholar 

  7. C McNeil (1998) ArticleTitleHeceptin raises its sights beyond advanced breast cancer J. Natl. Cancer Inst. 90 882–883 Occurrence Handle10.1093/jnci/90.12.882 Occurrence Handle1:STN:280:DyaK1c3pvFajtw%3D%3D Occurrence Handle9637135

    Article  CAS  PubMed  Google Scholar 

  8. S Tamrakar E Rubin JW Ludlow (2000) ArticleTitleRole of pRB dephosphorylation in cell cycle regulation Front Biosci. 5 D121–D137 Occurrence Handle1:CAS:528:DC%2BD3cXht1Shs7c%3D Occurrence Handle10702384

    CAS  PubMed  Google Scholar 

  9. CJ Sherr JM Roberts (1999) ArticleTitleCDK inhibitors: positive and negative regulators of G1-phase progression Genes Dev. 13 1501–1512 Occurrence Handle1:CAS:528:DyaK1MXktlOhsLs%3D Occurrence Handle10385618

    CAS  PubMed  Google Scholar 

  10. R Derynck L Choy (1998) Transforming growth factor-β, its receptors In The Cytokine Handbook EditionNumber3 Academic San Diego 593–636

    Google Scholar 

  11. AB Roberts MB Sporn (1990) The transforming growth factor-β AB Roberts MB Sporn (Eds) Peptide Growth Factors and Their Receptors Springer-Verlag Berlin

    Google Scholar 

  12. R Derynck XH Feng (1997) ArticleTitleTGF-β receptor signaling Biochim. Biophys. Acta 1333 F105–F150 Occurrence Handle1:CAS:528:DyaK2sXmtFKhsbg%3D Occurrence Handle9395284

    CAS  PubMed  Google Scholar 

  13. CH Heldin K Miyazono P ten Dijke (1997) ArticleTitleTGF-β signaling from cell membrane to nucleus through SMAD proteins Nature 390 465–471 Occurrence Handle10.1038/37284 Occurrence Handle1:CAS:528:DyaK2sXnvFyrtLo%3D Occurrence Handle9393997

    Article  CAS  PubMed  Google Scholar 

  14. R Derynck Y Zhang XH Feng (1998) ArticleTitleSmads: transcriptional activators of TGF-β responses Cell 95 737–740 Occurrence Handle10.1016/S0092-8674(00)81696-7 Occurrence Handle1:CAS:528:DyaK1MXivVGm Occurrence Handle9865691

    Article  CAS  PubMed  Google Scholar 

  15. Y Shi J Massague (2003) ArticleTitleMechanisms of TGF-β signaling from cell membrane to the nucleus Cell 113 685–700 Occurrence Handle10.1016/S0092-8674(03)00432-X Occurrence Handle1:CAS:528:DC%2BD3sXkvVekt7o%3D Occurrence Handle12809600

    Article  CAS  PubMed  Google Scholar 

  16. P Ten Dijke K Miyazono CH Heldin (2000) ArticleTitleSignaling inputs converge on nuclear effectors in TGF-β signaling Trends Biochem. Sci. 25 64–70 Occurrence Handle10.1016/S0968-0004(99)01519-4 Occurrence Handle1:CAS:528:DC%2BD3cXht1Krsrs%3D Occurrence Handle10664585

    Article  CAS  PubMed  Google Scholar 

  17. J Massagué S Blain R Lo (2000) ArticleTitleTGFβ signaling in growth control, cancer, and heritable disorders Cell 103 295–309 Occurrence Handle10.1016/S0092-8674(00)00121-5 Occurrence Handle11057902

    Article  PubMed  Google Scholar 

  18. I Reynisdottir J Massague (1997) ArticleTitleThe subcellular locations of p15(Ink4b) and p27(Kipl) coordinate their inhibitory interactions with cdk4 and cdk2 Genes Dev. 11 492–503 Occurrence Handle1:CAS:528:DyaK2sXhsFartbk%3D Occurrence Handle9042862

    CAS  PubMed  Google Scholar 

  19. M Laiho JA DeCaprio JW Ludlow et al. (1990) ArticleTitleGrowth inhibition by TGFβ linked to suppression of retinoblastoma protein phosphorylation Cell 62 175–185 Occurrence Handle10.1016/0092-8674(90)90251-9 Occurrence Handle1:CAS:528:DyaK3cXkvFWqtb4%3D Occurrence Handle2163767

    Article  CAS  PubMed  Google Scholar 

  20. RE Herrera TP Makela RA Weinberg (1996) ArticleTitleTGFβ-induced growth inhibition in primary fibroblasts requires the retinoblastoma protein Mol Biol Cell 7 1335–1342 Occurrence Handle1:CAS:528:DyaK28Xlslagsro%3D Occurrence Handle8885230

    CAS  PubMed  Google Scholar 

  21. XH Feng X Lin R Derynck (2000) ArticleTitleSmad2, Smad3 and Smad4 cooperate with Sp1 to induce p15Ink4B transcription in response to TGF-β EMBO J. 19 5178–5193 Occurrence Handle1:CAS:528:DC%2BD3cXnvF2qtLg%3D Occurrence Handle11013220

    CAS  PubMed  Google Scholar 

  22. A Iavarone J Massague (1997) ArticleTitleRepression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-β in cells lacking the CDK inhibitor p15 Nature 387 417–422 Occurrence Handle10.1038/387417a0 Occurrence Handle1:CAS:528:DyaK2sXjsVensb0%3D Occurrence Handle9163429

    Article  CAS  PubMed  Google Scholar 

  23. A Iavarone J Massague (1999) ArticleTitleE2F and histone deacetylase mediate transforming growth factor beta repression of cdc25A during keratinocyte cell cycle arrest Mol. Cell. Biol. 19 916–922 Occurrence Handle1:CAS:528:DyaK1MXhvFyhsg%3D%3D Occurrence Handle9858615

    CAS  PubMed  Google Scholar 

  24. Y Landesman M Pagano G Draetta et al. (1992) ArticleTitleModifications of cell cycle controlling nuclear proteins by transforming growth factor beta in the HaCaT keratinocyte cell line Oncogene 7 1661–1665 Occurrence Handle1:CAS:528:DyaK2cXisVahsQ%3D%3D Occurrence Handle1385861

    CAS  PubMed  Google Scholar 

  25. Y Geng RA Weinberg (1993) ArticleTitleTransforming growth factor beta effects on expression of G1 cyclins and cyclin-dependent protein kinases Proc. Natl. Acad. Sci. U.S.A. 90 10315–10319 Occurrence Handle1:CAS:528:DyaK2cXks1GmtA%3D%3D Occurrence Handle7694291

    CAS  PubMed  Google Scholar 

  26. KB Reddy BA Hocevar PH Howe (1994) ArticleTitleInhibition of G1 phase cyclin dependent kinases by transforming growth factor β1 J Cell. Biochem. 56 418–425 Occurrence Handle1:CAS:528:DyaK2MXitFygsrY%3D

    CAS  Google Scholar 

  27. I Barlat D Fesquet C Brechot et al. (1993) ArticleTitleLoss of the G1-S control of cyclin A expression during tumoral progression of Chinese hamster lung fibroblasts Cell Growth Differ. 4 105–113 Occurrence Handle1:CAS:528:DyaK3sXmt1ejtr8%3D Occurrence Handle8494781

    CAS  PubMed  Google Scholar 

  28. D Ralph M McClelland J Welsh (1993) ArticleTitleRNA fingerprinting using arbitrarily primed PCR identifies differentially regulated RNAs in mink lung (My1Lu) cells growth arrested by transforming growth factor β1 Proc Natl. Acad. Sci. U.S.A. 90 10710–10714 Occurrence Handle1:CAS:528:DyaK2cXisVCrsg%3D%3D

    CAS  Google Scholar 

  29. DJ Satterwhite ME Aakre AE Gorska et al. (1994) ArticleTitleInhibition of cell growth by TGFβ1 is associated with inhibition of B-myb and cyclin A in both BALB/MK and Mv1Lu cells Cell Growth Differ. 5 789–799 Occurrence Handle1:CAS:528:DyaK2cXlslWhtLc%3D Occurrence Handle7986745

    CAS  PubMed  Google Scholar 

  30. XH Feng EH Filvaroff R Derynck (1995) ArticleTitleTransforming growth factor-beta (TGF-beta)-induced down-regulation of cyclin A expression requires a functional TGF-beta receptor complex: characterization of chimeric and truncated type I and type II receptors J Biol. Chem. 270 24237–24245 Occurrence Handle1:CAS:528:DyaK2MXovVSgtbo%3D Occurrence Handle7592630

    CAS  PubMed  Google Scholar 

  31. ST Eblen MP Fautsch RJ Burnette et al. (1994) ArticleTitleCell cycle-dependent inhibition of p34cdc2 synthesis by transforming growth factor β1, in cycling epithelial cells Cell Growth Differ 5 109–116 Occurrence Handle1:CAS:528:DyaK2cXhvVeqsL4%3D Occurrence Handle8180123

    CAS  PubMed  Google Scholar 

  32. ME Ewen HK Sluss LL Whitehouse et al. (1993) ArticleTitleTGF-β inhibition of Cdk4 synthesis is linked to cell cycle arrest Cell 74 1009–1020 Occurrence Handle1:CAS:528:DyaK3sXlvFKlsr0%3D Occurrence Handle8402878

    CAS  PubMed  Google Scholar 

  33. A Koff M Ohtsuki K Polyak et al. (1993) ArticleTitleNegative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta Science 260 536–539 Occurrence Handle1:CAS:528:DyaK3sXisVynurc%3D Occurrence Handle8475385

    CAS  PubMed  Google Scholar 

  34. A Zentella FM Weis DA Ralph et al. (1991) ArticleTitleEarly gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function Mol. Cell. Biol. 11 4952–4958 Occurrence Handle1:CAS:528:DyaK3MXmt1Cktro%3D Occurrence Handle1922028

    CAS  PubMed  Google Scholar 

  35. MG Alexandrow M Kawabata M Aakre et al. (1995) ArticleTitleOverexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1 Proc Natl. Acad. Sci. U.S.A. 92 3239–3243 Occurrence Handle1:CAS:528:DyaK2MXltFSnt7c%3D Occurrence Handle7724545

    CAS  PubMed  Google Scholar 

  36. BJ Warner SW Blain J Seoane et al. (1999) ArticleTitleMyc downregulation by transforming growth factor beta required for activation of the p15(Ink4b) G(1) arrest pathway Mol. Cell Biol. 19 5913–5922 Occurrence Handle1:CAS:528:DyaK1MXlslSqur4%3D Occurrence Handle10454538

    CAS  PubMed  Google Scholar 

  37. GF Claassen SR Hann (2000) ArticleTitleA role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta-induced cell-cycle arrest Proc. Natl. Acad. Sci. U.S.A. 97 9498–9503 Occurrence Handle1:CAS:528:DC%2BD3cXmtVensLo%3D Occurrence Handle10920185

    CAS  PubMed  Google Scholar 

  38. P Sun P Dong K Dai et al. (1998) ArticleTitlep53-independent role of MDM2 in TGF-β1 resistance Science 282 2270–2272 Occurrence Handle1:CAS:528:DyaK1cXotFGjtrc%3D Occurrence Handle9856953

    CAS  PubMed  Google Scholar 

  39. XH Feng YY Liang M Liang et al. (2002) ArticleTitleDirect interaction of oncogenic c-Myc with tumor suppressors Smad2 and Smad3 to inhibit TGF-β-mediated induction of the CDK inhibitor p15INK4B Mol. Cell 9 133–143 Occurrence Handle1:CAS:528:DC%2BD38XhtVyjsLs%3D Occurrence Handle11804592

    CAS  PubMed  Google Scholar 

  40. J Wang L Sun L Meyeroff et al. (1995) ArticleTitleDemonstration that mutation of the type II TGF-β receptor inactivates its tumor suppressor activity in replication error-positive colon carcinoma cells J. Biol. Chem. 270 22044–22049 Occurrence Handle1:CAS:528:DyaK2MXotFait7g%3D Occurrence Handle7665626

    CAS  PubMed  Google Scholar 

  41. S Markowitz J Wang L Myeroff et al. (1995) ArticleTitleInactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability Science 268 1336–1338 Occurrence Handle1:CAS:528:DyaK2MXmtVartrk%3D Occurrence Handle7761852

    CAS  PubMed  Google Scholar 

  42. L Myeroff R Parsons SJ Kim et al. (1995) ArticleTitleA TGF-β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability Cancer Res. 55 5545–5547 Occurrence Handle1:CAS:528:DyaK2MXps1KrtLo%3D Occurrence Handle7585631

    CAS  PubMed  Google Scholar 

  43. L Sun G Wu JKV Willson et al. (1994) ArticleTitleExpression of transforming growth factor b type II receptor leads to reduced malignancy in human breast. cancer MCF-7 cells J. Biol. Chem. 269 26449–26455 Occurrence Handle1:CAS:528:DyaK2cXmt1Omtbo%3D Occurrence Handle7929366

    CAS  PubMed  Google Scholar 

  44. K Venkatasubbara S Ammanamanchi MG Brattain et al. (2001) ArticleTitleReversion of transcriptional repression of Sp1 by 5 aza-2′ deoxycytidine restores TGF-beta type II receptor expression in the pancreatic cancer cell line MIA PaCa-2 Cancer Res. 61 6239–6247 Occurrence Handle11507078

    PubMed  Google Scholar 

  45. DE Hansel SE Kern RH Hruban (2003) ArticleTitleMolecular pathogenesis of pancreatic cancer Annu. Rev. Genomics Hum. Genet. 4 237–256 Occurrence Handle1:CAS:528:DC%2BD3sXptFWmtbs%3D Occurrence Handle14527303

    CAS  PubMed  Google Scholar 

  46. L Sun G Wu JKV Willson et al. (1994) ArticleTitleExpression of transforming growth factor b type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells, J. Biol. Chem. 269 26449–26455 Occurrence Handle1:CAS:528:DyaK2cXmt1Omtbo%3D Occurrence Handle7929366

    CAS  PubMed  Google Scholar 

  47. GH Su R Bansal KM Murphy et al. (2001) ArticleTitleACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma Proc. Natl. Acad. Sci. U.S.A. 98 3254–3257 Occurrence Handle1:CAS:528:DC%2BD3MXit1alsb4%3D Occurrence Handle11248065

    CAS  PubMed  Google Scholar 

  48. SA Hahn AT Hoque CA Moskaluk et al. (1996) ArticleTitleHomozygous deletion map at 18q21.1 in pancreatic cancer Cancer Res. 56 490–494 Occurrence Handle1:CAS:528:DyaK28XnslOjsA%3D%3D Occurrence Handle8564959

    CAS  PubMed  Google Scholar 

  49. SA Hahn M Schutte AT Hoque et al. (1996) ArticleTitleDPC4, a candidate tumor suppressor gene at human chromosome 18q21.1 Science 271 350–353 Occurrence Handle1:CAS:528:DyaK28XlsFartg%3D%3D Occurrence Handle8553070

    CAS  PubMed  Google Scholar 

  50. GJ Riggins S Thiagalingam E Rozenblum et al. (1996) ArticleTitleMad-related genes in the human Nat. Genet. 13 347–349 Occurrence Handle10.1038/ng0796-347 Occurrence Handle1:CAS:528:DyaK28XktVegt7k%3D Occurrence Handle8673135

    Article  CAS  PubMed  Google Scholar 

  51. M Schutte RH Hruban L Hedrick et al. (1996) ArticleTitleDPC4 gene in various tumor types Cancer Res. 56 2527–2530 Occurrence Handle1:CAS:528:DyaK28XjtlCgtb0%3D Occurrence Handle8653691

    CAS  PubMed  Google Scholar 

  52. GJ Riggins KW Kinzler B Vogelstein et al. (1997) ArticleTitleFrequency of Smad gene mutations in human cancers Cancer Res. 57 2578–2580 Occurrence Handle1:CAS:528:DyaK2sXkt12rtLw%3D Occurrence Handle9205057

    CAS  PubMed  Google Scholar 

  53. S Thiagalingam C Lengauer FS Leach et al. (1996) ArticleTitleEvaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers Nat. Genet. 13 343–346 Occurrence Handle10.1038/ng0796-343 Occurrence Handle1:CAS:528:DyaK28XktVegt7s%3D Occurrence Handle8673134

    Article  CAS  PubMed  Google Scholar 

  54. AT Hoque SA Hahn M Schutte et al. (1997) ArticleTitleDPC4 gene mutation in colitis associated neoplasia Gut 40 120–122 Occurrence Handle1:CAS:528:DyaK2sXhvVeiu7c%3D Occurrence Handle9155588

    CAS  PubMed  Google Scholar 

  55. SK Kim Y Fan V Papadimitrakopulou et al. (1996) ArticleTitleDPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous carcinoma Cancer Res. 56 2519–2521 Occurrence Handle1:CAS:528:DyaK28XjtlCgtb8%3D Occurrence Handle8653689

    CAS  PubMed  Google Scholar 

  56. M Nagatake Y Takagi H Osada et al. (1996) ArticleTitleSomatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers Cancer Res. 56 2718–2720 Occurrence Handle1:CAS:528:DyaK28XjsFGku7w%3D Occurrence Handle8665501

    CAS  PubMed  Google Scholar 

  57. S Takakura A Okamoto M Saito et al. (1999) ArticleTitleAllelic imbalance in chromosome band 18q21 and SMAD4 mutations in ovarian cancers Genes Chromosomes Cancer 24 264–271 Occurrence Handle1:CAS:528:DyaK1MXht1enur8%3D Occurrence Handle10451707

    CAS  PubMed  Google Scholar 

  58. J Xu L Attisano (2000) ArticleTitleMutations in the tumor suppressors Smad2, Smad4 inactivate transforming growth factor beta signaling by targeting Smads to the ubiquitin-proteasome pathway Proc. Natl. Acad. Sci. U.S.A. 97 4820–4825 Occurrence Handle1:CAS:528:DC%2BD3cXivFKjuro%3D Occurrence Handle10781087

    CAS  PubMed  Google Scholar 

  59. X Lin M Liang YY Liang et al. (2003) ArticleTitleSUMO/Ubc9 promotes nuclear accumulation and metabolic stability of tumor suppressor Smad4 J. Biol. Chem. 278 31043–31048 Occurrence Handle1:CAS:528:DC%2BD3sXmtFeqtLs%3D Occurrence Handle12813045

    CAS  PubMed  Google Scholar 

  60. J Jen J Harper S Bigner et al. (1994) ArticleTitleDeletion of p16 and p15 genes in brain tumors Cancer Res. 54 6353–6358 Occurrence Handle1:CAS:528:DyaK2MXislamu7c%3D Occurrence Handle7987828

    CAS  PubMed  Google Scholar 

  61. T Nobori K Miura DJ Wu et al. (1994) ArticleTitleDeletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers Nature 368 753–756 Occurrence Handle1:STN:280:ByuB3czivVw%3D Occurrence Handle8152487

    CAS  PubMed  Google Scholar 

  62. JG Herman J Jen A Merlo et al. (1996) ArticleTitleHypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B Cancer Res. 56 722–727 Occurrence Handle1:CAS:528:DyaK28XhtVCls7Y%3D Occurrence Handle8631003

    CAS  PubMed  Google Scholar 

  63. PE Goretzki V Gorelov C Dotzenrath et al. (1996) ArticleTitleA frequent mutation/polymorphism in tumor suppressor gene INK4B (MTS-2) in papillary and medullary thyroid cancer Surgery 120 1081–1088 Occurrence Handle1:STN:280:ByiC3MnktFU%3D Occurrence Handle8957499

    CAS  PubMed  Google Scholar 

  64. H Suzuki X Zhou J Yin et al. (1995) ArticleTitleIntragenic mutations of CDKN2B and CDKN2A in preprimary human esophageal cancers Hum. Mol. Genet. 4 1883–1887 Occurrence Handle1:CAS:528:DyaK2MXoslykurY%3D Occurrence Handle8595411

    CAS  PubMed  Google Scholar 

  65. M Naumann N Savitskaia C Eilert et al. (1996) ArticleTitleFrequent codeletion of p16/MTS1 and p15/MTS2 and genetic alterations in p16/MTS1 in pancreatic tumors Gastroenterology 10 1215–1224

    Google Scholar 

  66. A Villanueva C Garcia AB Paules et al. (1998) ArticleTitleDisruption of the antiproliferative TGF-β signaling pathways in human pancreatic cancer cells Oncogene 17 1969–1978 Occurrence Handle1:CAS:528:DyaK1cXnt1Gltrc%3D Occurrence Handle9788440

    CAS  PubMed  Google Scholar 

  67. O Washimi M Nagatake H Osada et al. (1995) ArticleTitleIn vivo occurrence of p16 (MTS1) and p15 (MTS2) alterations preferentially in non-small cell lung cancers Cancer Res. 55 514–517 Occurrence Handle1:CAS:528:DyaK2MXjtlykt78%3D Occurrence Handle7834619

    CAS  PubMed  Google Scholar 

  68. A Batova MB Diccianni JC Yu et al. (1997) ArticleTitleFrequent and selective methylation of p15 and deletion of both p15 and p16 in T-cell acute lymphoblastic leukemia Cancer Res. 57 832–836 Occurrence Handle1:CAS:528:DyaK2sXhs1Kisro%3D Occurrence Handle9041181

    CAS  PubMed  Google Scholar 

  69. R Nakashima M Fujita T Enomoto et al. (1999) ArticleTitleAlteration of p16 and p15 genes in human uterine tumours Br. J. Cancer 80 458–467 Occurrence Handle1:CAS:528:DyaK1MXjtFyksrg%3D Occurrence Handle10408854

    CAS  PubMed  Google Scholar 

  70. EP Xing Y Nie Y Song et al. (1999) ArticleTitleMechanisms of inactivation of p14ARF, p15INK4b, and p16INK4a genes in human esophageal squamous cell carcinoma Clin. Cancer Res. 5 2704–2713 Occurrence Handle1:CAS:528:DyaK1MXntlGltLk%3D Occurrence Handle10537333

    CAS  PubMed  Google Scholar 

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  1. Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Room 131D, Houston, Texas 77030, USA

    Xia Lin Ph.D. & Xin-Hua Feng Ph.D.

  2. Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA

    Xin-Hua Feng Ph.D.

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Lin, X., Feng, XH. Abrogation of Transforming Growth Factor-β Signaling in Pancreatic Cancer. World J. Surg. 29, 312–316 (2005). https://doi.org/10.1007/s00268-004-7824-3

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