ALPHA TRANSFORMING GROWTH FACTORS IN RODENT AND HUMAN MAMMARY CARCINOMAS

正在进行实验，以确定分布和 转化生长因子α(TGFa)在正常和慢性肾小球疾病中的作用 恶性啮齿动物和人乳腺上皮细胞。主要 二甲基苯(α)菲(DMBA)和亚硝基甲基脲(NMU) 诱导的大鼠乳腺腺癌具有免疫反应性和 从生物学上讲，TGFAlpha。一个特定的4.8kb的TGFpha mRNA物种 可在DMBA和NMU诱导的大鼠乳腺中检测到 肿瘤。卵巢切除后，患者的性激素水平下降了5到10倍。 DMBA肿瘤组织中TGFa mRNA的表达NOG 8小鼠乳房 将含有糖链基因的重组质粒导入上皮细胞。 与点突变c-HA-ras基因连锁的皮质激素诱导型MMTv-LTR 原癌基因在添加了 地塞米松(Dex)作用于这些细胞。在接受德克斯治疗后，有 是p21ras蛋白和c-Ha-ras mRNA的快速诱导 在3到5小时内。在这段时间里，有一个坐标 TGFn mRNA表达水平的增加以及随后的 增加转化生长因子α蛋白的产量。人类乳房 癌细胞株也产生TGFα，并具有TGFAlpha MRNA.在MCF-7细胞中，转化生长因子α和转化生长因子的水平 雌激素可增强α-mRNA的表达。治疗 用多克隆抗人转化生长因子α抗体或与 抗人表皮生长因子受体的单抗将抑制 这些细胞在体外的生长。转化生长因子α水平升高 在大约65%的原发肿瘤中可以检测到转化生长因子αmRNA 人类乳房肿瘤。这些结果表明，转化生长因子α可能是 作为一种啮齿动物亚群的自分泌生长因子 人乳腺肿瘤细胞和雌激素或激活或过度- Ras原癌基因的表达可能控制肿瘤的产生 这种生长因素。

Experiments are being conducted to determine the distribution and role of transforming growth factor alpha (TGFa ) in normal and malignant rodent and human mammary epithelial cells. Primary dimethylbenz (alpha) anthracene (DMBA) and nitrosomethylurea (NMU) induced rat mammary adenocarcinomas possess immunoreactive and biologically TGFalpha. A specific 4.8 Kb TGFalpha mRNA species could be detected in the DMBA - and NMU - induced rat mammary tumors. Ovariectomy produced a five to tenfold decrease in the expression of TGFa mRNA in the DMBA tumors. Nog 8 mouse mammary epithelial cells transfected with a plasmid containing a gluco- corticoid inducible MMTv-LTR linked to the point-mutated c-HA-ras proto-oncogene become transformed following the addition of dexamethesone (dex) to these cells. Following dex treatment, there is a rapid induction of the p21ras protein and of c-Ha-ras mRNA within 3 to 5 hours. During this interval there is a co- ordinate increase in the level of expression of TGFn mRNA and a subsequent increase in the production of TGFalpha protein. Human breast cancer cell lines are also producing TGFalpha and possess TGFalpha mRNA. In MCF-7 cells, the level of production of TGF alpha and TGF alpha mRNA expression can be enhanced by estrogens. Treatment of MCF-7 cells with a polyclonal anti-human TGF alpha antibody or with a monoclonal antibody against the human EGF receptor will inhibit the growth of these cells in vitro. Elevated levels of TGF alpha and TGF alpha mRNA can be detected in approximately 65% of primary human breast tumors. These results suggest that TGF alpha may function as an autocrine growth factor for a subset of rodent and human mammary tumor cells and that estrogens or activation or over- expression of a ras protooncogene may control the production of this growth factor.