Summary
Overexpression of proto-oncogenes (c-onc) may be involved in the initiation and progression of human neoplasia. We investigated the mRNA expression of the protooncogenes c-myc, c-fos, c-neu (erb B-2) and Ha-ras in 12 cutaneous melanocytic lesions (four dermal naevi, seven melanomas; one cutaneous metastatis of melanoma) and in normal skin (five cases) by Northern blot analysis; mRNA expression levels were quantified by densitometry of the specific bands. The expression of c-myc mRNA was higher in naevi than in melanomas, whereas c-fos mRNA expression was significantly higher in melanomas than in naevi. No significant differences were detected in the c-neu and Ha-ras mRNA levels in naevi and melanomas. The expression of c-neu mRNA was higher in normal skin than in the melanocytic lesions examined. Our results suggest that enhanced c-myc and c-fos expression may play an important role in the growth of melanocytic naevi and melanomas. The overexpression of c-fos may be involved in the progression of a particular subset of melanoma. Activation of Ha-ras and the c-neu gene, as determined by mRNA overexpression, does not seem to play a significant role in the progression of cutaneous pigmented lesions. Expression of c-neu may have an important function in the proliferation and/or differentiation of normal cells of the epidermis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albino AP (1988) The status of oncogenes in malignant melanoma. In: Bagnara JT (ed) Advances in pigment cell research. Liss, New York, pp 361–390
Albino AP, Strange R Le, Oliff AF, Furth ME, Old LJ (1984) Transforming ras genes from human melanoma: a manifestigation of tumor hetereogeneity? Nature 308:69–72
Alitalo M, Schwab M (1986) Oncogene amplification in tumor cells. Adv Cancer Res 47:235–282
Balmain A, Ramsden M, Bowden GT, Smith J (1984) Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 307:658–660
Chirgwin JM, Przybyla AE, Mac Donald RJ, Rutter WJ (1979) Isolation of biologically active RNA from source enriched in ribonuclease. Biochemistry 18:5294–5297
Curran T, Miller AD, Zokas L, Verma I (1984) Viral and cellular fos proteins: a comparative analysis. Cell 36:259–268
Dalla Favera R, Martinotti S, Gallo RC, Erikson J, Croce CM (1983) Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B cell lymphomas. Science 219:963
Eisenmann RN, Tachibana CY, Abrams HD, Hann SR (1985) V-myc and c-myc encoded proteins are associated with the nuclear matrix. Mol Cell Biol 5:114–126
Fellbaum C, Radaszkiewicz T, Ruhri C, Pütz B, Moosberger I, Höfler H (1990) C-myc mRNA overexpression in high grade non Hodgkin lymphomas. Virchows Arch [B] (in press)
Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311:433–437
Harper JH, Reynolds SH, Greenhalg DA, Strickland JE, Lacal JC, Yuspa SH (1987) Analysis of the rasH oncogene and its p21 product in chemically induced skin tumors and tumor-derived cell lines. Carcinogenesis 8:1821–1825
Höfler H (1990) Oncogene and receptor expression. In: Seifert G (ed) Current topics in pathology cell receptor. Springer, Berlin Heidelberg New York (in press)
Israel MA, Helman LJ, Miser J (1987) Patterns of protooncogene expression: A novel approach to the development of tumor markers. In: DeVita VT, Hellman S, Rosenberg SA (eds) Important advances in oncology 1987. Lippincott, Philadelphia, pp 87–104
Krujier W, Cooper JA, Hunter T, Verma JM (1984) PDGF induces rapid but transient expression of the c-fos gene. Nature 312:711–716
Maniatis T, Fritsch EF, Sambrock J (1982) Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor
Monnat M, Tardy S, Sagara P, Diggelmann H, Costa J (1987) Prognostic implications of expression of the cellular genes myc, fos, Ha-ras and Ki-ras in colon carcinoma. Int J Cancer 40:239–299
Muschl R, Liotta LA (1988) Role of oncogenes in metastases. Carcinogenesis 9:705–710
Nanus DM, Cordon-Cardo C, Albino AP (1987) Expression of ras proto-oncogene product in premalignant and malignant melanoma tissues. (abstract) Proceedings of the Annual Meeting of the American Association for Cancer Research.
Nau MM, Brooks BJ, Carney DN, Gazdar AF, Minna JD (1986) Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci USA 83:1092–1096
Ogiso Y, Oikawa T, Kondo N, Kuzumaki N, Sugihara T, Ohvra T (1988) Expression of proto-oncogenes in normal and tumor tissues of human skin. J Invest Dermatol 90:842–844
Padua RA, Barras N, Currie GA (1984) A novel transforming gene in a human malignant cell line. Nature 311:671–673
Padua RA, Barras NC, Currie GA (1985) Activation of N-ras in a human melanoma cell line. Mol Cell Biol 5:582–585
Peris K, Pütz B, Ruhri C, Höfler H (1989) Detection of point mutations of the ras gene in paraffin embedded tissue sections by polymerase chain reaction. Verh Dtsch Ges Pathol 73:657
Quintanilla M, Brown K, Ramsden M, Balmain A (198)6) Carcinogen-specific mutation and amplification of Haras during mouse skin carcinogenesis. Nature 322:78–80
Rabbits PH, Watson JV, Lamond A, Forster A, Stinson MA, Evan G, Fisher W, Atherton E, Sheppard S, Rabbits TH (1985) Metabolism of c-myc gene products: c-myc mRNA and protein expression in the cell cycle. EMBO J 4:2009–2015
Reddy EP, Reynolds RK, Santos E, Barbacid M (1982) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300:149–152
Riou G, Barrois M, Le MG, George M, Le Doussal V, Haie C (1987) C-myc proto-oncogene expression and prognosis in early carcinoma of the uterine cervix. Lancet I:761–764
Schechter AL, Hunge MC, Vaidyanathan L, Weiberg RA, Yang-Feng TL, Francke U, Ullrich A, Coussens L (1985) The neu gene: an erb-B homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229:976–978
Sekiya T, Fushimi M, Hori H, Hirohashi S, Nishimura S, Sugimura T (1984) Molecular cloning and the total nucleotide sequence of the human c-Ha-ras 1 gene activated in a melanoma from a Japanese patient. Proc Natl Acad Sci USA 81:4771–4775
Slamon DJ, Cline MJ (1984) Expression of cellular oncogenes during embryonic and fetal development of the mouse. Proc Natl Acad Sci USA 246:7141–7145
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the erB-2/neu oncogene. Science 235:177–182
Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712
Sobel ME (1990) Metastasis suppressor genes. J Nat. Cancer Inst. 82:267–276
Stidzinski GP, Brevli ZS, Feldman SC, Watt RA (1986) Participation of c-myc protein in DNA synthesis of human cells. Science 234:467–470
Sweet W, Yokoyama S, Kamata T, Feramisco JR, Rosenberg M, Gross M (1984) The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature 311:273–275
Weinberg RA (1987) The action of oncogenes in the cytoplasm and nucleus. Science 230:313–327
Yasuda H, Kobayashi H, Ohkawara A, Kuzumaki N (1989) Differential expression of ras oncogene products among the types of human melanomas and melanocytic nevi. J Invest Dermatol 93:54–59