Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors.

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-1, 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-1 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-proliferative and early- to mid-secretory phases and high expression in late-secretory and early-proliferative 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.

• Authors: E M Rutanen, T Nyman, P Lehtovirta, M Ammälä, F Pekonen
• Journal: International journal of cancer (Int J Cancer) Vol. 59 Issue 3 Pg. 307-12 (Nov 01 1994) ISSN: 0020-7136 [Print] United States
• PMID: 7523316 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• DNA Primers
• Insulin-Like Growth Factor Binding Protein 1
• RNA, Messenger
• Somatomedins

Topics

• Adenocarcinoma (metabolism, pathology)
• Aged
• Base Sequence
• Carrier Proteins (genetics, metabolism)
• DNA Primers
• Endometrial Neoplasms (metabolism, pathology)
• Endometrium (metabolism)
• Female
• Gene Expression
• Humans
• Insulin-Like Growth Factor Binding Protein 1
• Middle Aged
• Molecular Sequence Data
• Neoplasm Staging
• Polymerase Chain Reaction
• RNA, Messenger (metabolism)
• Risk Factors
• Somatomedins (genetics, metabolism)