Jindal S K, Ishii E, Letarte M, Vera S, Teerds K J, Dorrington J H
Banting & Best Department of Medical Research, University of Toronto, Ontario, Canada.
Biol Reprod. 1995 May;52(5):1027-37. doi: 10.1095/biolreprod52.5.1027.
The surface epithelium plays an important role in normal ovarian physiology: the cells proliferate in the vicinity of the developing preovulatory follicle to accommodate the increase in follicular size, and to repair the surface after ovulation. These bouts of mitotic activity in vivo must be strictly regulated by the activity of growth factors and their receptors. Since transforming growth factor alpha (TGF alpha) has been identified as a growth-promoting factor for normal surface epithelial cells from human ovaries and ovarian surface epithelial cell lines, we have examined the regulation of the TGF alpha gene in HEY cells, a surface epithelial cell line derived from a human ovarian carcinoma. Treatment of HEY cells for 60 h with estradiol-17 beta, dihydrotestosterone, or progesterone at concentrations ranging from 5 x 10(-8) to 5 x 10(-6) M did not influence the level of the 4.5-kb transcript for TGF alpha. Treatment of HEY cells with TGF alpha increased the steady-state levels of TGF alpha mRNA, indicating that an autoregulatory mechanism could result in overexpression of TGF alpha. TGF beta, a known growth inhibitor of ovarian surface epithelial cells, decreased the steady-state levels of TGF alpha mRNA, suggesting a mechanism by which the levels of TGF alpha and mitotic activity could be regulated. HEY cells, like the human surface epithelial cells from which they were derived, were found by quantitative polymerase chain reaction (PCR) to contain TGF beta 1 mRNA. The TGF beta 1 mRNA was translated into immunoreactive TGF beta 1, indicating that TGF beta can act in an autocrine manner. By use of quantitative PCR, HEY cells were shown to express the genes for the TGF beta receptor II, betaglycan and endoglin. By cross-linking, these components of the TGF beta receptor system were found to bind TGF beta 1. This is the first demonstration of expression of functional TGF beta receptors in HEY cells and represents the first demonstration in an ovarian cell system. In summary, our findings suggest that the levels of TGF alpha and the cell growth of normal and transformed surface epithelial cells from human ovaries may be regulated by the interaction of autoregulatory mechanisms involving TGF alpha and TGF beta ligand-receptor systems.
细胞在发育中的排卵前卵泡附近增殖，以适应卵泡大小的增加，并在排卵后修复表面。体内这些有丝分裂活动的周期必须受到生长因子及其受体活性的严格调控。由于转化生长因子α（TGFα）已被确定为人类卵巢和卵巢表面上皮细胞系正常表面上皮细胞的促生长因子，我们研究了TGFα基因在HEY细胞中的调控，HEY细胞是一种源自人卵巢癌的表面上皮细胞系。用浓度范围为5×10⁻⁸至5×10⁻⁶M的雌二醇-17β、二氢睾酮或孕酮处理HEY细胞60小时，并未影响TGFα 4.5-kb转录本的水平。用TGFα处理HEY细胞增加了TGFα mRNA的稳态水平，表明一种自动调节机制可能导致TGFα的过度表达。TGFβ是已知的卵巢表面上皮细胞生长抑制剂，它降低了TGFα mRNA的稳态水平，提示了一种调节TGFα水平和有丝分裂活动的机制。通过定量聚合酶链反应（PCR）发现，HEY细胞与它们所源自的人类表面上皮细胞一样，含有TGFβ1 mRNA。TGFβ1 mRNA被翻译成具有免疫反应性的TGFβ1，表明TGFβ可以以自分泌方式发挥作用。通过定量PCR显示，HEY细胞表达TGFβ受体II、β聚糖和内皮糖蛋白的基因。通过交联发现，TGFβ受体系统的这些成分能结合TGFβ1。这是首次证明HEY细胞中功能性TGFβ受体的表达，也是首次在卵巢细胞系统中的证明。总之，我们的研究结果表明，人卵巢正常和转化表面上皮细胞的TGFα水平和细胞生长可能受到涉及TGFα和TGFβ配体-受体系统的自动调节机制相互作用的调控。
