KARYOTYPIC ANALYSIS OF MALIGNANT SKIN TUMORS OF TG-AG (V-HA-RAS) AND FVB MICE

将v-Ha-ras(TG.AC小鼠；Zeta-珠蛋白促进的v-Ha-ras)插入FVB 小鼠消除致癌物启动和促进的启动步骤 小鼠皮肤肿瘤的发生。以及v-Ha-ras和v-Ha-ras的点突变 C-Ha-ras，6号和7号染色体三体，c-Ha-ras等位基因失衡，以及 7号染色体上的杂合性缺失已被报道与肿瘤有关 从良性乳头状瘤进展为鳞状细胞癌或梭形细胞癌 细胞瘤。肿瘤促进剂的序贯局部应用 TG.AC(Zeta-珠蛋白促进的v-Ha-ras启动子)转基因小鼠导致 诱导乳头状瘤后出现盘状软组织 有溃烂表面的肿块。这些肿瘤的核型分析 表明10号和6号染色体的三体模式高度一致 和13号染色体单体。来自原代的纺锤形细胞 培养物移植到9至11天龄时具有高度致瘤性。 同基因受者，产生大的圆盘状或大的椭圆形 在大约两周内使肿瘤溃烂。西方对中国的分析 这些移植瘤表明转基因(v-Ha-ras)具有很高的 与转基因动物正常皮肤相比，表达并诱导 乳头状瘤。这些结果表明，这些梭形细胞瘤 由插入v-Ha-ras转基因引发，随后是化学 促进涉及复杂的染色体排列，这可能是重要的 鉴定与皮肤相关的其他癌基因和/或肿瘤抑制基因 肿瘤发生学。

Insertion of v-Ha-ras (TG.AC mice; zeta-globin promoted v-Ha-ras) into FVB mice eliminates the initiation step in carcinogen initiated and promoted mouse skin tumorigenesis. Along with point mutations in both v-Ha-ras and c-Ha-ras, trisomies of chromosomes 6 and 7, c-Ha-ras allelic imbalance, and LOH on chromosome 7 have been reported to be associated with tumor progression from benign papillomas to squamous cell carcinomas or spindle cell tumors. Sequential topical application of tumor promoting agents to TG.AC (zeta-globin promoted v-Ha-ras initiated) transgenic mice resulted in papilloma induction followed by the appearance of disc-shaped soft tissue masses with an ulcerating surface. Karyotypic analysis of these tumors indicated a highly consistent pattern of trisomy of chromosomes 10 and 6 and monosomy of chromosome 13. The spindle shaped cells from primary cultures were highly tumorigenic when transplanted to 9 to 11 day old syngeneic recipients, resulting in large disc-shaped or larger oval shaped ulcerating tumors within approximately two weeks. Western analysis of these transplanted tumors indicate that the transgene (v-Ha-ras) is highly expressed compared to normal skin from transgenic animals and induced papillomas. These results indicate that these spindle shaped cell tumors initiated by insertion of this v-Ha-ras transgene followed by chemical promotion involve complex chromosome arrangements which may be important in identifying other oncogenes and/or tumor suppressor genes involved in skin tumorigenesis.