TRANSFORMING GROWTH FACTORS FROM HUMAN MAMMARY TISSUES

转化人类乳腺组织的生长因子

• 批准号: 3963054
• 负责人: D S SALOMON
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3963054
• 关键词: breast neoplasms; chemical carcinogenesis; clone cells; complementary DNA; deficient growth media; electrofocusing; epidermal growth factor; fibroblasts; gene expression; growth factor; growth media; high performance liquid chromatography; human milk; human tissue; mammary epithelium; molecular weight; oncogenes; transforming growth factors

Experiments are being conducted to determine the distribution and role of alpha transforming growth factors (AlphaTGFs) 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 AlphaTGFs 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 AlphaTGF cDNA probes but not in the DMBA-I or NMU-II tumors. Ovariectomy produced a two to three-fold decrease in the level of AlphaTGFs in the primary DMBA tumors which was preceeded by a loss in the expression of AlphaTGF 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 AlphaTGF mRNA. Human breast cancer cell lines are also producing AlphaTGF and possess AlphaTGF mRNA. In MCF-7 cells, the level of production of AlphaTGF can be enhanced by estrogens. Elevated levels of immunoreactive AlphaTGF and AlphaTGF mRNA can be detected in approximately 50% of primary human breast carcinomas. There is a strong positive correlation between the presence of AlphaTGF mRNA and the presence of functional estrogen receptors in a subset of these tumors.

正在进行实验以确定其分布和作用 正常和恶性的α转化生长因子（AlphaTGFs） 啮齿动物和人类乳腺上皮细胞。 基本的 二甲基苯并(α)蒽 (DMBA) 和亚硝基甲基脲 (NMU) 大鼠 乳腺癌的生物学特征是其三到七倍 活性和免疫反应性 AlphaTGF 优于可移植 DMBA-I 和 NMU-II 癌。 此外，可以在以下细胞中检测到特定的 5.0 kb mRNA 种类： 多聚 A(+) RNA 杂交后的原发性 DMBA 和 NMU 肿瘤 人类和小鼠 AlphaTGF cDNA 探针，但不在 DMBA-I 或 NMU-II 中 肿瘤。 卵巢切除术使卵巢功能水平下降两到三倍 原发性 DMBA 肿瘤中的 AlphaTGFs 在此之前发生了损失 AlphaTGF mRNA 的表达。 小鼠乳腺上皮细胞 用点突变的 c-Ha-ras 原癌基因转化 NMuMG/rasH 细胞， 对 EGF 的生长促进作用产生抵抗，因为这些细胞 合成 AlphaTGF mRNA 的能力增强。 人体乳房 癌细胞系也产生 AlphaTGF 并拥有 AlphaTGF mRNA。 在 MCF-7 细胞中，可以通过以下方式增强 AlphaTGF 的产生水平： 雌激素。 免疫反应性 AlphaTGF 和 AlphaTGF mRNA 水平升高 大约 50% 的人类原发性乳腺癌中可检测到。 AlphaTGF 的存在之间存在很强的正相关性 mRNA 和其中一部分中功能性雌激素受体的存在 肿瘤。