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Carcinogenesis |
Departments of Immunology-178 [F. M. S.] and Cancer Biology [S. P., A. S. M., C. K. D.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Pangea Phytoceuticals, Harlingen, Texas 78550 [R. P. P.]
A major obstacle in understanding the etiology of malignant melanoma is the lack of mouse models and transplantable cell lines. We have recently developed a model of primary melanoma in C3H mice induced by ethanol and UV light. The present study characterizes three cell lines, SM190.2, SM190.626, and SD0302, derived from two melanomas produced in the dorsal skin of two C3H mice treated thrice weekly for 2833 weeks with UV radiation and ethanol. In both tumors, the N-ras oncogene was mutated. Tumor SM190 lacked exon 2 of the p16INK4a tumor suppressor gene. Cell line SM190.2, which was derived from tumor SM190, produced pigmented tumors when transplanted into syngeneic severe combined immunodeficient mice and normal mice. None of the cell lines produced metastases. All three cell lines were highly aneuploid, even at low passage numbers. SM190.2 and SD0302 cells contained an interstitial deletion in the long arm of chromosome 4, where the p16INK4a gene resides, and SM190.2 had an additional segment in chromosome 6. The third cell line, SM190.626, had three consistent Robertsonian translocation markers involving chromosomes 7, 14, and 17. The translocation involving mouse chromosome 14 may prove especially valuable because translocations in this chromosome are associated with metastatic behavior. These reagents will provide opportunities to search for new tumor suppressor genes that may contribute to the growth and metastasis of primary melanoma.
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