POLYAMINES AND EPITHELIAL TUMORIGENESIS

描述：鸟氨酸脱羧酶（ODC）是在 TPA治疗，但不是在用其他药物治疗后 增生/非促进剂。 ODC在某些肿瘤中也升高。 ODC水平升高导致多胺升高。 转氨酶（TG） 将多胺连接到各种蛋白质上，这些蛋白质可能介导分化 的表皮细胞。 在这个R 01中，它在许多方面似乎是一个 R29（1990-95）的延续，主要研究者希望 研究ODC表达和多胺是否可以与ras协同作用， 引起表皮肿瘤和/或影响角质形成细胞的分化。 （一） 将含有ODC基因的逆转录病毒载体导入几种细胞中， 类型，这些类型被评估为在SC后引起肿瘤的能力。 注射 BK-1细胞不含激活的c-ras，没有产生肿瘤， 而SP-1和308细胞含有激活的c-ras，产生肿瘤。 所有 三个显示ODC和多胺升高。 这表明ODC升高 单独的表达可以至少部分地促进。 (2)ODC 过表达影响DNA合成、生长、分化和TG 水平（一般书写--细胞类型不清楚？）。 (3)转基因小鼠 用角蛋白[K6 ]启动子驱动的ODC基因表达产生。 他们出生体重低，在2个月时脱发。 一个 异常真皮发展为大的角蛋白填充的良性滤泡囊肿 在正常的表皮下 年老的老鼠发展为良性角化癌。 可以通过施用ODC特异性抑制剂来预防脱发， DFMO，从出生起就一直如此。 有三个具体目标：（1）ODC可以 过表达与v-ras协同作用，增强肿瘤形成潜能 BK-1细胞？ (2)ODC转基因小鼠将与 携带活化的v-ras的转基因小鼠（TG.AC）。同时含有这两种基因的小鼠 转基因会导致表皮肿瘤 (3)不适当的毒品和犯罪问题办公室活动 影响正常和起始角质形成细胞的分化， 评估。

DESCRIPTION: Ornithine decarboxylase (ODC) is synthesized early after treatment with TPA, but not after treatment with other hyperplastic/non-promoting agents. ODC is also elevated in certain tumors. Elevated ODC levels lead to elevated polyamines. Transglutaminase (TG) links polyamines to various proteins, which may mediate the differentiation of epidermal cells. In this R01, which in many ways appears to be a continuation of an R29 (1990-95), the principal investigator wishes to investigate whether ODC expression and polyamines can cooperate with ras to cause epidermal tumors and/or affect differentiation of keratinocytes. (1) A retroviral vector containing the ODC gene was introduced into several cell types, which were assessed for the ability to cause tumors following sc injection. BK-1 cells, which contain no activated c-ras, gave no tumors, while SP-1 and 308 cells, which contain activated c-ras, gave tumors. All three showed elevated ODC and polyamines. This suggests that elevated ODC expression alone can be promoting at least partially. (2) ODC overexpression affected DNA synthesis, growth, differentiation, and TG levels (written generally--cell type unclear?). (3) Transgenic mice were generated with ODC gene expression driven from a keratin [K6 ]promoter. They have low birth weight and experience hair loss at 2 months. An abnormal dermis develops with large keratin-filled, benign, follicular cysts underneath a normal epidermis. Older mice develop benign keratocarcinomas. Hair loss can be prevented by administering the ODC specific inhibitor, DFMO, continuously from birth. There are 3 Specific Aims: (1) Can ODC overexpression cooperate with v-ras to enhance the tumor forming potential of BK-1 cells? (2) The ODC transgenic mice will be cross-bred with transgenic mice carrying activated v-ras (TG.AC). Will mice containing both transgenes develop epidermal tumors? (3) How inappropriate ODC activity affect differentiation of normal and initiated keratinocytes will be assessed.