Identification of differentially expressed messenger RNAs in human melanocytes and melanoma cells.
The phenotype of malignant lesions is a reflection of genetic events altering the RNA and protein expression patterns of normal cells. We have investigated RNA expression patterns distinguishing normal melanocytes (FM 902), a primary melanoma cell line (WM 793), and its variant cell line (1205-LU), selected for metastatic phenotype in athymic mice. Using mRNA differential display, we identified 42 different cDNA PCR products with cell line-specific expression patterns. Direct sequence analysis matched approximately 50% of the cDNA PCR products with gene sequences accessible in DNA databases. Among the known genes, two functionally distinct groups were recognized: (a) genes encoding ribosomal and mitochondrial proteins that were predominantly up-regulated in the malignant cells; and (b) genes encoding modulators of the immune response. Among the immunomodulators, the T-cell antigen MART-1 and the protease inhibitor alpha2-macroglobulin were detected in the melanocyte cell line but not in the tumor cells. By contrast, mRNAs for the complement inhibitor CD59 and the cytokine IL-1beta were found to be overexpressed in the malignant melanoma cells. RNA slot blot hybridization on a larger panel of melanocyte and melanoma cell lines confirmed differential expression of 15 of 42 genes including MART-1, alpha2-macroglobulin, and CD59. This molecular screening approach identified also three partially characterized and three novel sequences with differential expression patterns in normal and malignant melanocytes.
Simon
H G
HG
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.
Risse
B
B
Jost
M
M
Oppenheimer
S
S
Kari
C
C
Rodeck
U
U
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005069:Evaluation Studies as Topic; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008544:Melanocytes / Q000378:metabolism* / Q000502:physiology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012333:RNA, Messenger