ALPHA TRANSFORMING GROWTH FACTORS IN RODENT AND HUMAN MAMMARY CARCINOMAS

正在进行实验以确定分布 和α转化生长因子（α TGF）在 正常和恶性啮齿动物和人乳腺上皮 细胞 伯二甲基苯并（α）蒽（DMBA）和 亚硝基甲基脲（NMU）大鼠乳腺癌具有 生物活性和免疫活性 与可移植的DMBA-I和NMU-II癌相比。 此外，在大肠杆菌中可以检测到一种特异的5.0kb mRNA种类， 原发性DMBA和NMU肿瘤， poly A（+）RNA与人和小鼠α TGF cDNA探针结合， 而不是DMBA-I或NMU-II肿瘤。 卵巢切除术产生了一个 两到三倍的α TGF水平下降， 原发性DMBA肿瘤，其前期是由于 α TGF mRNA的表达。 小鼠乳腺上皮 它们被点突变的c-Ha-ras基因转化 原癌基因，NMuMG/rasH细胞，变得耐药， EGF的作用，因为这些细胞有 增加合成α TGF mRNA的能力。 人类 乳腺癌细胞系也产生α TGF， α TGF mRNA。 在MCF-7细胞中， TGF α和TGF α mRNA表达可通过以下方式增强： 雌激素并被抗雌激素阻断。 此外，治疗 MCF-7细胞与多克隆抗人TGF α抗体或 抗人EGF受体的单克隆抗体 在体外抑制这些细胞的生长。 水平升高 可检测到免疫反应性α TGF和α TGF mRNA 在大约65%的原发性人类乳腺癌中。 这是一个很强的正相关性之间的存在 α TGF mRNA和功能性雌激素的存在 这些肿瘤的一个子集中的受体。 这些结果表明 TGF α可能作为一种自分泌生长因子， 啮齿动物和人乳腺肿瘤细胞亚群， 雌激素反应性，并且激活或过度表达 ras原癌基因也可能控制TGF α的水平 生产

Experiments are being conducted to determine the distribution and role of alpha transforming growth factors (alpha TGFs) in normal and malignant rodent and human mammary epithelial cells. Primary dimethylbenz (alpha) anthracene (DMBA) and nitrosomethylurea (NMU) rat mammary adenocarcinomas possess three to seven-fold more biologically active and immunoreactive alpha TGFs than transplantable DMBA-I and NMU-II carcinomas. Moreover, a specific 5.0 kb mRNA species could be detected in the primary DMBA and NMU tumors following hybridization of poly A(+) RNA to a human and mouse alpha TGF cDNA probes but not in the DMBA-I or NMU-II tumors. Ovariectomy produced a two to three-fold decrease in the level of alpha TGFs in the primary DMBA tumors which was preceeded by a loss in the expression of alpha TGF mRNA. Mouse mammary epithelial which have been transformed with a point-mutated c-Ha-ras proto-oncogene, NMuMG/rasH cells, become resistant to the growth promoting effects of EGF because these cells have an increased capacity to synthesize alpha TGF mRNA. Human breast cancer cell lines are also producing alpha TGF and possess alpha TGF mRNA. In MCF-7 cells, the level of production of alpha TGF and TGF alpha mRNA expression can be enhanced by estrogens and blocked by anti-estrogens. In addition 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 immunoreactive alpha TGF and alpha TGF mRNA can be detected in approximately 65% of primary human breast carcinomas. These is a strong positive correlation between the presence of alpha TGF mRNA and the presence of functional estrogen receptors in a subset of these tumors. These results suggest that TGF alpha may function as an autocrine growth factor for a subset of rodent and human mammary tumor cells which are estrogen responsive and that the activation or overexpression of a ras proto-oncogene may also control the level of TGF alpha production.