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

TG-AG (V-HA-RAS) 和 FVB 小鼠恶性皮肤肿瘤的核型分析

• 批准号: 3841046
• 负责人: J E FRENCH
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841046
• 关键词: autologous transplantation; chemical carcinogen; chemical carcinogenesis; cutaneous papilloma; genetically modified animals; karyotype; laboratory mouse; neoplasm /cancer genetics; neoplasm /cancer transplantation; oncogenes; transposon /insertion element; trisomy; tumor promoters; western blottings

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.

将v-Ha-ras（TG.AC小鼠; ζ-珠蛋白促进v-Ha-ras）插入FVB中 小鼠消除了致癌物引发和促进的起始步骤 小鼠皮肤肿瘤发生。 沿着v-Ha-ras和 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号染色体上的洛缺失与肿瘤的发生有关 从良性乳头状瘤进展为鳞状细胞癌或梭形细胞癌 细胞肿瘤 序贯局部应用肿瘤促进剂， TG.AC（zeta-珠蛋白促进的v-Ha-ras启动的）转基因小鼠导致 乳头状瘤诱导后出现盘状软组织 表面溃烂的肿块。 这些肿瘤的核型分析 表明10号和6号染色体的三体性模式高度一致 和13号染色体的单体性。 原代培养的梭形细胞 当移植到9至11日龄时，培养物具有高度致瘤性 同系受体，导致大的圆盘形或更大的椭圆形 在大约两周内使肿瘤溃烂。 西方分析 这些移植的肿瘤表明转基因（v-Ha-ras）是高表达的， 与来自转基因动物的正常皮肤相比， 乳头状瘤 这些结果表明，这些梭形细胞肿瘤 通过插入该v-Ha-ras转基因启动，然后用化学方法 促进涉及复杂的染色体排列， 鉴定皮肤中涉及的其它癌基因和/或肿瘤抑制基因 肿瘤发生