편평상피암에서의 c-myc, erb B 및 EGF-Receptor 유전자의 세포-분자생물학적 특성

Abstract

Background : Oncogenes and EGF-Receptor(EGFR) may be involved n different stages of the multistep carcinogenesis process. A specific pattern of karyotypic abnormalities in solid tumors can be detected by cytogenetic methods. Onjective : This study is intnded to observe the cytomolecular kiologic chracterization of c-myc, erb B and EGFR genes in squasnous cell carcinoma(SCC) of the skin and cervix. Methods : We have eytogenet,ically examined the short-term culturs from SCC. The rearrangement, amplification or expressi.on of erb B, c-myc, and EGFR genes were studied by Southern blot, analysis of genomic DNA and by slot blot analysis of tota! RNA extracted from biopsies of normal skin and SCC tissues. EGFR expression was examined immunohistochemially using monoclonal antibodies and the localizat,ion of the c-myc oncogene mRNA by in situ hybridization. Results : A remarkably structural aberration was del 6(q21-qter) counted 20 metaphases among 28 metaphases ana1yzed. In nunierical aberration, all chromosomes were lost or gained randomly. Amenploid including triploid and tetraploid were observed in 8 metaphases, 6 tumor cells contained marker chromosome. In Southern blot analysis, rearrangement and amglificaton of EGFR in primary squamous cell carcinoma of cervix uteri and skin respectively. In slot blot analysis, the levels of c-myc, erb B and EGFR mRNA increaaed respectively 3.5, 2.5 and 2.8 times in SCC when compared to normal tissues. In immunoperoxidase stain, EGFR was present, in SCC where keratinocytes with strong cyto-plasmic staining but no membr, line labelling, where as in normal skin the were primarily present in t,he membrane and cytoplasm of basal cells. In situ hybridization with c-myc cDNAs allowed detection of grains representative of biotin labelled cDNA-mRNA hybrids in the frozden section of SCC tissues. Conclusion : These results suggest that specific patterns of karyotypir abnormalites, rearrangement, or amplification of EGFR gene, and overexpression of oncogenes and EGFR gene may be associated with the carcinogenesis of SCC.