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转化生长因子α在正常人类卵巢表面上皮及卵巢癌细胞中的定位与作用

Transforming growth factor alpha localization and role in surface epithelium of normal human ovaries and in ovarian carcinoma cells.

作者信息

Jindal S K, Snoey D M, Lobb D K, Dorrington J H

机构信息

Banting & Best Department of Medical Research, University of Toronto, Ontario, Canada.

出版信息

Gynecol Oncol. 1994 Apr;53(1):17-23. doi: 10.1006/gyno.1994.1080.

DOI:10.1006/gyno.1994.1080
PMID:8175016
Abstract

Transforming growth factor alpha (TGF alpha) has been localized by immunohistochemistry in the ovarian surface epithelial (OSE) cells of sections from normal human ovaries and in epithelial cells of surface crypts. An ovarian cancer cell line (HEY) derived from the surface epithelium of a human ovary also exhibited intense staining for the TGF alpha peptide. Using Northern analysis, HEY cells were shown to express a 4.5-kb transcript of TGF alpha, indicating that the TGF alpha peptide was synthesized by these cells and not taken up from the serum in the culture medium and sequestered by the cells. This was confirmed using a radioimmunoassay, which showed that HEY cells in culture secrete TGF alpha peptide, both as a soluble (0.12 +/- 0.02 ng/mg protein) and as a membrane-anchored (0.06 +/- 0.006 ng/mg protein) form. In both normal OSE cells and HEY cells, TGF alpha acted as a growth promoter: TGF alpha significantly stimulated [3H]thymidine incorporation into DNA of both primary cultures of normal OSE cells (2.7-fold) and of HEY cells (2-fold). This study provides the first demonstration of TGF alpha immunostaining in normal surface epithelial cells and in HEY cells, and suggests that TGF alpha, localized in normal and transformed OSE, is an autocrine growth promoter for these cells.

摘要

通过免疫组织化学方法,在正常人卵巢切片的卵巢表面上皮(OSE)细胞以及表面隐窝的上皮细胞中发现了转化生长因子α(TGFα)。源自人卵巢表面上皮的卵巢癌细胞系(HEY)对TGFα肽也表现出强烈染色。通过Northern分析表明,HEY细胞表达4.5kb的TGFα转录本,这表明TGFα肽是由这些细胞合成的,而不是从培养基中的血清摄取并被细胞截留。使用放射免疫测定法证实了这一点,该方法表明培养中的HEY细胞分泌TGFα肽,以可溶性形式(0.12±0.02 ng/mg蛋白质)和膜锚定形式(0.06±0.006 ng/mg蛋白质)存在。在正常OSE细胞和HEY细胞中,TGFα均作为生长促进剂:TGFα显著刺激[3H]胸苷掺入正常OSE细胞原代培养物(2.7倍)和HEY细胞(2倍)的DNA中。本研究首次证明了TGFα在正常表面上皮细胞和HEY细胞中的免疫染色,并表明定位于正常和转化的OSE中的TGFα是这些细胞的自分泌生长促进剂。

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Br J Cancer. 1996 Feb;73(3):301-6. doi: 10.1038/bjc.1996.53.