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Genetic Basis of Human Breast Cancer Metastasis

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Abstract

Once cancer cells have spread and formed secondary masses, breast cancers are largely incurable even with state-of-the-art medicine. To improve diagnosis and therapy, better markers are needed to distinguish cells which have a high probability for causing clinically relevant, macroscopic metastases. In this review, we summarize the several genes that regulate breast cancer metastasis. Two categories of genes are presented—metastasis activator (ras, MEK1, mta1, proteinases, adhesion molecules, chemoattractants/receptors, autotaxin, PKC, S100A4, RhoC, osteopontin) and metastasis suppressor (Nm23, E-cadherin, TIMPs, KiSS1, Kai1, Maspin, MKK4, BRMS1). While the mechanisms of action for most of these genes are not fully elucidated, some clues are emerging and are presented.

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REFERENCES

  1. D. R. Welch and L. L. Wei (1998). Genetic and epigenetic regulation of human breast cancer progression and metastasis. Endocr. Relat. Cancer 5:155-197.

    Google Scholar 

  2. B. A. Yoshida, M. Sokoloff, D. R. Welch, and C. W. Rinker-Schaeffer (2000). Metastasis-suppressor genes: A review and perspective on an emerging field. J. Natl. Cancer Inst. 92:1717-1730.

    Google Scholar 

  3. D. R. Welch and C. W. Rinker-Schaeffer (1999). What defines a useful marker of metastasis in human cancer? J. Natl. Cancer Inst. 91:1351-1353.

    Google Scholar 

  4. I. J. Fidler and R. Radinsky (1990). Genetic control of cancer metastasis. J. Natl. Cancer Inst. 82:166-168.

    Google Scholar 

  5. S. F. Goldberg, J. F. Harms, K. Quon, and D. R. Welch (1999). Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate. Clin. Exp. Metastasis 17: 601-607.

    Google Scholar 

  6. M. A. Chekmareva, M. M. Kadkhodaian, C. M. P. Hollowell, H. Kim, B. A. Yoshida, H. H. Luu, W. M. Stadler, and C.W. Rinker-Schaeffer (1998). Chromosome 17-mediated dormancy of AT6.1 prostate cancer micrometastases. Cancer Res. 58:4963-4969.

    Google Scholar 

  7. D. R. Welch (1997). Technical considerations for studying cancer metastasis in vivo. Clin. Exp. Metastasis 15:272-306.

    Google Scholar 

  8. J. E. Price, A. Polyzos, R. D. Zhang, and L. M. Daniels (1990). Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice. Cancer Res. 50:717-721.

    Google Scholar 

  9. J. E. Price and R.D. Zhang (1990). Studies of human breast cancer metastasis using nude mice. Cancer Metastasis Rev. 8:285-297.

    Google Scholar 

  10. S. M. Frisch and E. Ruoslahti (1997). Integrins and anoikis. Curr. Opin. Cell Biol. 9:701-706.

    Google Scholar 

  11. B. Mann, A. Gratchev, C. Bohm, M. L. Hanski, H. D. Foss, G. Demel, B. Trojanek, I. Schmidt-Wolf, H. Stein, E. O. Riecken, H. J. Buhr, and C. Hanski (1999). FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas. Br. J. Cancer 79:1262-1269.

    Google Scholar 

  12. T. A. Springer (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: A multistep paradigm. Cell 76:301-314.

    Google Scholar 

  13. T. Krause and G. A. Turner (1999). Are selectins involved in metastasis? Clin. Exp. Metastasis 17:183-192.

    Google Scholar 

  14. C. C. Kumar (1998). Signaling by integrin receptors. Oncogene 17:1365-1373.

    Google Scholar 

  15. A. Raz and R. Lotan (1987). Endogenous galactoside-binding lectins: A new class of functional tumor cell surface molecules related to metastasis. Cancer Metastasis Rev. 6:433-452.

    Google Scholar 

  16. A. K. Perl, P. Wilgenbus, U. Dahl, H. Semb, and G. Christofori (1998). A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature (London) 392:190-193.

    Google Scholar 

  17. T. Akimoto, S. Kawabe, A. Grothey, and L. Milas (1999). Low E-cadherin and beta-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas. Clin. Exp. Metastasis 17:171-176.

    Google Scholar 

  18. K. Brew, D. Dinakarpandian, and H. Nagase (2000). Tissue inhibitors of metalloproteinases: Evolution, structure and function. Biochim. Biophys. Acta Protein Struct. Mol. Enzymol. 1477:267-283.

    Google Scholar 

  19. A. R. Nelson, B. Fingleton, M. L. Rothenberg, and L. M. Matrisian (2000). Matrix metalloproteinases: Biologic activity and clinical implications. J. Clin. Oncol. 18:1135-1149.

    Google Scholar 

  20. A. F. Chambers and L. M. Matrisian (1997). Changing views of the role of matrix metalloproteinases in metastasis. J. Natl. Cancer Inst. 89:1260-1270.

    Google Scholar 

  21. P. A. Andreasen, L. Kjoller, L. Christensen, and M. J. Duffy (1997). The urokinase-type plasminogen activator system in cancer metastasis: A review. Int. J. Cancer 72:1-22.

    Google Scholar 

  22. J. E. Koblinski, M. Ahram, and B. F. Sloane (2000). Unraveling the role of proteases in cancer. Clin. Chim. Acta 291:113-135.

    Google Scholar 

  23. M. L. Stracke, T. Clair, and L. A. Liotta (1997). Autotaxin, tumor motility-stimulating exophosphodiesterase. Adv. Enzyme Regul. 37:135-144.

    Google Scholar 

  24. K. Lamszus, L. Jin, A. Fuchs, E. Shi, S. Chowdhury, Y. Yao, P. J. Polverini, J. Laterra, I. D. Goldberg, and E. M. Rosen (1997). Scatter factor stimulates tumor growth and tumor angiogenesis in human breast cancers in the mammary fat pads of nude mice. Lab. Invest. 76:339-353.

    Google Scholar 

  25. K. Jacob, M. Webber, D. Benayahu, and H. K. Kleinman (1999). Osteonectin promotes prostate cancer cell migration and invasion: Apossible mechanism for metastasis to bone. Cancer Res. 59:4453-4457.

    Google Scholar 

  26. A. Müller, B. Homey, H. Soto, N. F. Ge, D. Catron, M. E. Buchanan, T. McClanahan, E. Murphy, W. Yuan, S. N. Wagner, J. L. Barrera, A. Mohar, E. Verástegui, and A. Zlotnik (2001). Involvement of chemokine receptors in breast cancer metastasis. Nature (London) 410:50-56.

    Google Scholar 

  27. Y. Toh, S. D. Pencil, and G. L. Nicolson (1994). A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J. Biol. Chem. 269:22958-22963.

    Google Scholar 

  28. A. Neri, D. R. Welch, T. Kawaguchi, and G. L. Nicolson (1982). Development and biologic properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma. J. Natl. Cancer Inst. 68:507-517.

    Google Scholar 

  29. M. D. Martin, K. Fischbach, C. K. Osborne, S. K. Mohsin, D. C. Allred, and P. O'Connell (2001). Loss of heterozygosity events impeding breast cancer metastasis contain the MTA1 gene. Cancer Res. 61:3578-3580.

    Google Scholar 

  30. Y. Xue, J. Wong, G. T. Moreno, M. K. Young, J. Cote, and W. Wang (1998). NURD, a novel complex with both ATPdependent chromatin-remodeling and histone deacetylase activities. Mol. Cell 2:851-861.

    Google Scholar 

  31. Y. Zhang, H. H. Ng, H. Erdjument-Bromage, P. Tempst, A. Bird, and D. Reinberg (1999). Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 13:1924-1935.

    Google Scholar 

  32. M. Schwirzke, S. Schiemann, A. U. Gnirke, and U. H. Weidle (1999). New genes potentially involved in breast cancer metastasis. Anticancer Res. 19:1801-1814.

    Google Scholar 

  33. S. C. Kiley, K. J. Clark, S. K. Duddy, D. R. Welch, and S. Jaken (1999). Increased protein kinase C± in mammary tumor cells: Relationship to transformation and metastatic progression. Oncogene 18:6748-6757.

    Google Scholar 

  34. S. C. Kiley, K. J. Clark, M. Goodnough, D. R. Welch, and S. Jaken (1999). Protein kinase C delta involvement in mammary tumor cell metastasis. Cancer Res. 59:3230-3238.

    Google Scholar 

  35. A. F. Chambers and A. B. Tuck (1993). Ras-responsive genes and tumor metastasis. Crit. Rev. Oncog. 4:95-114.

    Google Scholar 

  36. C. P. Webb, G. A. Taylor, M. Jeffers, M. Fiscella, M. Oskarsson, J. H. Resau, and G. F. Vande Woude (1998). Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/ metastasis. Oncogene 17:2019-2025.

    Google Scholar 

  37. D. R. Welch, T. Sakamaki, R. Pioquinto, T. O. Leonard, S. F. Goldberg, Q. Hon, M. Rieber, M. Strasberg-Rieber, D. J. Hicks, J. V. Bonventre, and A. Alessandrini (2000). Transfection of constitutively active Mek1 confers tumorigenic and metastatic potentials to NIH3T3 cells. Cancer Res. 60:1552-1556.

    Google Scholar 

  38. A. A. P. Schmitz, E. E. Govek, B. Böttner, and L. Van Aelst (2000). Rho GTPases: Signaling, migration, and invasion. Exp. Cell Res. 261:1-12.

    Google Scholar 

  39. E. E. Sander and J.G. Collard (1999). Rho-like GTPases: Their role in epithelial cell-cell adhesion and invasion. Eur. J. Cancer [A] 35:1302-1308.

    Google Scholar 

  40. K. L. Van Golen, Z. F. Wu, X. T. Qiao, L. W. Bao, and S. D. Merajver (2000). RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Res. 60:5832-5838.

    Google Scholar 

  41. A. J. Oates, R. Barraclough, and P. S. Rudland (1997). The role of osteopontin in tumorigenesis and metastasis. Invasion Metastasis 17:1-15.

    Google Scholar 

  42. H. Singhal, D. S. Bautista, K. S. Tonkin, F. P. O'Malley, A. B. Tuck, A. F. Chambers, and J. F. Harris (1997). Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin. Cancer Res. 3:605-611.

    Google Scholar 

  43. A. B. Tuck, F. P. O'Malley, H. Singhal, J. F. Harris, K. S. Tonkin, N. Kerkvliet, Z. Saad, G. S. Doig, and A. F. Chambers (1998). Osteopontin expression in a group of lymph node negative breast cancer patients. Int. J. Cancer 79:502-508.

    Google Scholar 

  44. Y.W. Kim, Y. K. Park, J. Lee, S.W. Ko, and M. H. Yang (1998). Expression of osteopontin and osteonectin in breast cancer. J. Korean Med. Sci. 13:652-657.

    Google Scholar 

  45. C. Gruss and M. Herlyn (2001). Role of cadherins and matrixins in melanoma. Curr. Opin. Oncol. 13:117-123.

    Google Scholar 

  46. T. A. Graham, C. Weaver, F. Mao, D. Kimelman, and W. Q. Xu (2000). Crystal structure of a β-catenin/Tcf complex. Cell 103:885-896.

    Google Scholar 

  47. G. Berx, A. M. Cleton-Jansen, K. Strumane, W. J. F. De Leeuw, F. Nollet, F. Van Roy, and C. Cornelisse (1996). E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13:1919-1925.

    Google Scholar 

  48. J. R. Graff, E. Gabrielson, H. Fujii, S. B. Baylin, and J. G. Herman (2000). Methylation patterns of the E-cadherin 5'CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J. Biol. Chem. 275:2727-2732.

    Google Scholar 

  49. K. M. Hajra, X. Ji, and E. R. Fearon (1999). Extinction of E-cadherin expression in breast cancer via a dominant repression pathway acting on proximal promoter elements. Oncogene 18:7274-7279.

    Google Scholar 

  50. G. Christofori and H. Semb (1999). The role of the celladhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem. Sci. 24:73-76.

    Google Scholar 

  51. M. Toi, S. Ishigaki, and T. Tominaga (1998). Metalloproteinases and tissue inhibitors of metalloproteinases. Breast Cancer Res. Treat. 52:113-124.

    Google Scholar 

  52. A. H. Ree, V. A. Florenes, J. P. Berg, G. M. Maelandsmo, J. M. Nesland, and O. Fodstad (1997). High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin. Cancer Res. 3:1623-1628.

    Google Scholar 

  53. G. Y. Li, R. Fridman, and H. R. C. Kim (1999). Tissue inhibitor of metalloproteinase-1 inhibits apoptosis of human breast epithelial cells. Cancer Res. 59:6267-6275.

    Google Scholar 

  54. K. McCarthy, T. Maguire, G. McGreal, E. McDermott, N. O'Higgins, and M. J. Duffy (1999). High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer. Int. J. Cancer 84:44-48.

    Google Scholar 

  55. J. M. Kozlowski, I. J. Fidler, D. Campbell, Z. Xu, M. E. Kaighn, and I. R. Hart (1984). Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res. 44:3522-3529.

    Google Scholar 

  56. W. H. Yu, S. S. C. Yu, Q. Meng, K. Brew, and J. F. Woessner Jr. (2000). TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J. Biol. Chem. 275:31226-31232.

    Google Scholar 

  57. J. M. Freije, N. J. MacDonald, and P. S. Steeg (1998). Nm23 and tumour metastasis: Basic and translational advances. Biochem. Soc. Symp. 63:261-271.

    Google Scholar 

  58. D. Lombardi, M. L. Lacombe, and M. G. Paggi (2000). nm23: Unraveling its biological function in cell differentiation. J. Cell Physiol. 182:144-149.

    Google Scholar 

  59. M. T. Hartsough, S. E. Clare, M. Mair, A. G. Elkahloun, D. Sgroi, C. K. Osborne, G. Clark, and P. S. Steeg (2001). Elevation of breast carcinoma Nm23-H1 metastasis suppressor gene expression and reduced motility by DNAmethylation inhibition. Cancer Res. 61:2320-2327.

    Google Scholar 

  60. E. H. Postel, S. J. Berberich, S. J. Flint, and C. A. Ferrone (1993). Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science (Washington, D.C.) 261:478-480.

    Google Scholar 

  61. N. J. MacDonald, A. De La Rosa, M. A. Benedict, J. M. Freije, H. Krutsch, and P. S. Steeg (1993). A serine phosphorylation of Nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential. J. Biol. Chem. 268:25780-25789.

    Google Scholar 

  62. A. L. Perraud, V. Weiss, and R. Gross (1999). Signalling pathways in two-component phosphorelay systems. Trends Microbiol. 7:115-120.

    Google Scholar 

  63. A. R. Shenoy (2000). His kinase or mine? Histidine kinases through evolution. J. Biosci. 25:317-322.

    Google Scholar 

  64. S. I. Aizawa, C. S. Harwood, and R. J. Kadner (2000). Signaling components in bacterial locomotion and sensory reception. J. Bacteriol. 182:1459-1471.

    Google Scholar 

  65. R. Sager, S. Sheng, P. Pemberton, and M. J. Hendrix (1996). Maspin: A tumor suppressing serpin. Curr. Top. Microbiol. Immunol. 213:51-64.

    Google Scholar 

  66. F. E. Domann, J. C. Rice, M. J. C. Hendrix, and B.W. Futscher (2000). Epigenetic silencing of maspin gene expression in human breast cancers. Int. J. Cancer 85:805-810.

    Google Scholar 

  67. S. Zucker, J. Cao, and W.T. Chen (2000). Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 19:6642-6650.

    Google Scholar 

  68. J. R. Starkey, H. L. Hosick, D. R. Stanford, and H. D. Liggitt (1984). Interaction of metastatic tumor cells with bovine lens capsule basement membrane. Cancer Res. 44:1585-1594.

    Google Scholar 

  69. E. Friedman, C. Urmacher, and S. Winawer (1984). A model for human colon carcinoma evolution based on the differential response of cultured preneoplastic, premalignant and malignant cells to 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 44:1568-1578.

    Google Scholar 

  70. M. Zhang, O. Volpert, Y. H. Shi, and N. Bouck (2000). Maspin is an angiogenesis inhibitor. Nat. Med. 6:196-199.

    Google Scholar 

  71. J. LeCouter, J. Kowalski, J. Foster, P. Hass, Z. M. Zhang, L. Dillard-Telm, G. Frantz, L. Rangell, L. DeGuzman, G. A. Keller, F. Peale, A. Gurney, K. J. Hillan, and N. Ferrara (2001). Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412:877-884.

    Google Scholar 

  72. M. Zhang, Y. Shi, D. Magit, P. A. Furth, and R. Sager (2000). Reduced mammary tumor progression in WAP-TAg/WAPmaspin bitransgenic mice. Oncogene 19:6053-6058.

    Google Scholar 

  73. S. M. North and G. L. Nicolson (1985). Heterogeneity in the sensitivities of the 13762NF rat mammary adenocarcinoma cell clones to cytolysis mediated by extra-and intratumoral macrophages. Cancer Res. 45:1453-1458.

    Google Scholar 

  74. J. J. Li, N. H. Colburn, and L.W. Oberley (1998). Maspin gene expression in tumor suppression induced by overexpressing manganese-containing superoxide dismutase cDNA in human breast cancer cells. Carcinogenesis 19:833-839.

    Google Scholar 

  75. J.-T. Dong, P. W. Lamb, C. W. Rinker-Schaeffer, J. Vukanovic, T. Ichikawa, J. T. Isaacs, and J. C. Barrett (1995). KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science (Washington, D.C.) 268:884-886.

    Google Scholar 

  76. K. K. Phillips, A. E. White, D. J. Hicks, D. R. Welch, J. C. Barrett, L. L. Wei, and B. E. Weissman (1998). Correlation between reduction of metastasis in the MDA-MB-435 model system and increased expression of the Kai-1 protein. Mol. Carcinog. 21:111-120.

    Google Scholar 

  77. X. H. Yang, D. R. Welch, K. K. Phillips, B. E. Weissman, and L. L. Wei (1997). KAI1, a putative marker for metastatic potential in human breast cancer. Cancer Lett. 119:149-155.

    Google Scholar 

  78. C. I. Huang, N. Kohno, E. Ogawa, M. Adachi, T. Taki, and M. Miyake (1998). Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. Am. J. Pathol. 153:973-983.

    Google Scholar 

  79. X. Yang, L. Wei, C. Tang, R. Slack, E. Montgomery, and M. Lippman (2000). KAI1 protein is down-regulated during the progression of human breast cancer. Clin. Cancer Res. 6:3424-3429.

    Google Scholar 

  80. P. Jackson, D. Millar, E. Kingsley, G. Yardley, K. Ow, S. Clark, and P. J. Russell (2000). Methylation of a CpG island within the promoter region of the KAI1 metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines. Cancer Lett. 157:169-176.

    Google Scholar 

  81. T. Mashimo, M. Watabe, S. Hirota, S. Hosobe, K. Miura, P. J. Tegtmeyer, C.W. Rinker-Schaeffer, and K. Watabe (1998). The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53. Proc. Natl. Acad. Sci.U.S.A. 95:11307-11311.

    Google Scholar 

  82. C. Duriez, N. Falette, U. Cortes, C. Moyret-Lalle, and A. Puisieux (2000). Absence of p53-dependent induction of the metastatic suppressor KAI1 gene after DNA damage. Oncogene 19:2461-2464.

    Google Scholar 

  83. A. West, P. J. Vojta, D. R. Welch, and B. E. Weissman (1998). Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1). Genomics 54:145-148.

    Google Scholar 

  84. J.-H. Lee and D. R. Welch (1997). Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Res. 57:2384-2387.

    Google Scholar 

  85. A. I. Muir, L. Chamberlain, N. A. Elshourbagy, D. Michalovich, D. J. Moore, A. Calamari, P. G. Szekeres, H. M. Sarau, J. K. Chambers, P. Murdock, K. Steplewski, U. Shabon, J. E. Miller, S. E. Middleton, J.G. Darker, C.G. C. Larminie, S. Wilson, D. J. Bergsma, P. Emson, R. Faull, K. L. Philpott, and D. C. Harrison (2001). AXOR12: A novel human G protein-coupled receptor, activated by the peptide KiSS-1. J. Biol. Chem. 276:28969-28975.

    Google Scholar 

  86. T. Ohtaki, Y. Shintani, S. Honda, H. Matsumoto, A. Hori, K. Kanehashi, Y. Torao, S. Kumano, Y. Takatsu, Y. Matsuda, Y. Ishibashi, T. Watanabe, M. Asada, T. Yamada, M. Suenaga, C. Kitada, S. Usuki, T. Kurokawa, H. Onda, O. Nishimura, and M. Fujino (2001). Metastasis suppressor gene KiSS1 encodes peptide ligand of a G-protein-coupled receptor. Nature (London) 411:613-617.

    Google Scholar 

  87. C. H. Yan, H. Wang, and D. D. Boyd (2001). KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappaB binding to the promoter as a consequence of IB α-induced block of p65/p50 nuclear translocation. J. Biol. Chem. 276:1164-1172.

    Google Scholar 

  88. C. W. Rinker-Schaeffer, A. L. Hawkins, N. Ru, J. Dong, G. Stoica, C. A. Griffin, T. Ichikawa, J. C. Barrett, and J. T. Isaacs (1994). Differential suppression of mammary and prostate cancer metastasis by human chromosomes 17 and 11. Cancer Res. 54:6249-6256.

    Google Scholar 

  89. B. A. Yoshida, Z. Dubauskas, M. A. Chekmareva, T. R. Christiano, W. M. Stadler, and C. W. Rinker-Schaeffer (1999). Mitogen-activated protein kinase kinase 4/stress-activated protein/Erk kinase 1 (MKK4/SEK1), a prostate cancer metastasis suppressor gene encoded by human chromosome 17. Cancer Res. 59:5483-5487.

    Google Scholar 

  90. B. A. Yoshida, Z. Dubauskas, M. A. Chekmareva, M. M. Zaucha, T. R. Christiano, A. P. Christiano, W. M. Stadler, and C.W. Rinker-Schaeffer (1999). Identification and characterization of candidate prostate cancer metastasis-suppressor genes encoded on human chromosome 17. Cancer Res. 59:5483-5487.

    Google Scholar 

  91. H. L. Kim, D. J. Van der Griend, X. Yang, D. A. Benson, Z. Dubauskas, B. A. Yoshida, M. A. Chekmareva, Y. Ichikawa, M. H. Sokoloff, P. Zhan, T. Karrison, A. Lin, W. M. Stadler, T. Ichikawa, M. A. Rubin, and C. W. Rinker-Schaeffer (2001). Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers. Cancer Res. 61:2833-2837.

    Google Scholar 

  92. M. J. Seraj, R. S. Samant, M. F. Verderame, and D. R. Welch (2000). Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13. Cancer Res. 60:2764-2769.

    Google Scholar 

  93. D. R. Welch, M.J. Seraj, R. S. Samant, T.O. Leonard, J.F. Harms, and M. F. Verderame (1999). BrMS1-A human breast cancer metastasis-suppressor gene encoded on chromosome 11q13.1-q13.2. Clin. Cancer Res. 5:66.

    Google Scholar 

  94. M. M. Saunders, M. J. Seraj, Z. Y. Li, Z. Y. Zhou, C. R. Winter, D. R. Welch, and H. J. Donahue (2001). Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication. Cancer Res. 61:1765-1767.

    Google Scholar 

  95. F. Shirasaki, M. Takata, N. Hatta, and K. Takehara (2001). Loss of expression of the metastasis suppressor gene KiSS1 during melanoma progression and its association with LOH of chromosome 6q16.3-q23. Cancer Research 61:7422-7425.

    Google Scholar 

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  1. Jake Gittlen Cancer Research Institute, College of Medicine, Penn State University, Hershey, Pennsylvania

    Michael T. Debies & Danny R. Welch

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  1. Michael T. Debies
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Debies, M.T., Welch, D.R. Genetic Basis of Human Breast Cancer Metastasis. J Mammary Gland Biol Neoplasia 6, 441–451 (2001). https://doi.org/10.1023/A:1014739131690

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