Suppressed expression of insulin‐like growth factor binding protein‐1 mRNA in the endometrium: A molecular mechanism associating endometrial cancer with its risk factors
- 1 November 1994
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 59 (3) , 307-312
- https://doi.org/10.1002/ijc.2910590303
Abstract
The insulin‐like growth factor (IGF) system is thought to function as a mediator of steroid hormone actions in the endometrium. IGFs (IGF‐I and IGF‐II) are also potent mitogens in endometrial cancer. The biological actions of IGFs are modulated by specific binding proteins (IGFBP)—6 cloned and sequenced so far—which may either inhibit or enhance the effects of IGF at the cellular level. In the endometrium, IGFBP‐1 gene expression is stimulated by progesterone and inhibited by insulin, while IGFBP‐1 inhibits the mitogenic action of IGF‐I. In this study, we used a quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) to investigate IGFBP‐I, IGFBP‐2, IGFBP‐4, IGFBP‐5 and IGFBP‐6 gene expression in endometrial cancer tissues. Endometrial cancer tissue samples were collected from 20 women (aged 54–79 yrs) with stage I to II well‐differentiated endometrial adenocarcinoma. Samples of normal endometrium (n = 14) obtained from women undergoing tubal ligation in various phases of the menstrual cycle, and normal early‐pregnancy endometrium (decidua) were studied for comparison. In endometrial cancer tissues, the IGFBP‐I mRNA was undetectable or minimally expressed when studied by RT‐PCR. The mean (+SD) levels of IGFBP‐2 and IGFBP‐4 and IGFBP‐5 mRNAs in endometrial cancer tissues did not differ from those in normal endometrium, in which no cyclic variation was observed, suggesting that the genes encoding IGFBP‐2, IGFBP‐4 and IGFBP‐5 are not hormonally regulated in the endometrium. The IGFBP‐6 mRNA expression showed a significant cyclic variation in normal endometrium, with low levels in late‐prolitferative and early‐ to mid‐secretory phases and high expression in late‐secretory and early‐prolitferative phases. In endometrial cancer tissues, the mean IGFBP‐6 mRNA level was similar to that in cycling endometrium during the peri‐ovulatory period. In summary, a continuous stimulation of the endometrial epithelial cells by IGFs with suppressed IGFBP‐1 expression may lead to an imbalance in the IGF system of the endometrium and trigger an uncontrolled cell proliferation, ultimately resulting in malignant transformation.Keywords
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