Lippman M E, Dickson R B, Gelmann E P, Rosen N, Knabbe C, Bates S, Bronzert D, Huff K, Kasid A
Medical Breast Cancer Section, National Cancer Institute, Bethesda, MD 20892.
J Steroid Biochem. 1988;30(1-6):53-61. doi: 10.1016/0022-4731(88)90076-3.
The mechanisms by which human breast cancers regulate their own growth have been studied by us in an in vitro model system. We showed that specific growth factors (IGF-I, TGF alpha, PDGF) are secreted by human breast cancer cells. A variety of experiments suggest that they are involved in tumor growth and progression. These activities are induced by estradiol in hormone-dependent breast cancer cells and secreted constitutively by estrogen-independent cells. Concentrates of conditioned medium derived from breast cancer cells can induce the growth of hormone-dependent cells in vivo in athymic nude mice. Hormone-dependent breast cancer cells also secrete TGF beta. TGF beta is growth inhibitory. Growth inhibitors such as antiestrogens or glucocorticoids increase TGF beta secretion. An antiestrogen-resistant mutant of MCF-7 cells does not secrete TGF beta when treated with antiestrogen, but is growth inhibited when treated with exogenous TGF beta. Thus, TGF beta functions as a negative autocrine growth regulator and is probably responsible for some of the growth inhibitory effects of antiestrogens.
我们在体外模型系统中研究了人类乳腺癌调节自身生长的机制。我们发现人类乳腺癌细胞会分泌特定的生长因子（胰岛素样生长因子-I、转化生长因子α、血小板衍生生长因子）。一系列实验表明，这些生长因子参与肿瘤的生长和进展。在激素依赖性乳腺癌细胞中，这些活性由雌二醇诱导产生，而在雌激素非依赖性细胞中则持续分泌。源自乳腺癌细胞的条件培养基浓缩物可在无胸腺裸鼠体内诱导激素依赖性细胞的生长。激素依赖性乳腺癌细胞也分泌转化生长因子β。转化生长因子β具有生长抑制作用。抗雌激素或糖皮质激素等生长抑制剂会增加转化生长因子β的分泌。MCF-7细胞的抗雌激素抗性突变体在用抗雌激素处理时不分泌转化生长因子β，但在用外源性转化生长因子β处理时生长受到抑制。因此，转化生长因子β作为一种负性自分泌生长调节因子，可能是抗雌激素某些生长抑制作用的原因。
