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Cancer Causes & Control
Published in: Cancer Causes & Control 6/2016

Open Access 01-06-2016 | Original paper

Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors

Authors: Melissa A. Merritt, Howard D. Strickler, Mark H. Einstein, Hannah P. Yang, Mark E. Sherman, Nicolas Wentzensen, Jurriaan Brouwer-Visser, Maria Jose Cossio, Kathleen D. Whitney, Herbert Yu, Marc J. Gunter, Gloria S. Huang

Published in: Cancer Causes & Control | Issue 6/2016

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Abstract

Purpose

Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology.

Methods

We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data. Endometrial tissue mRNA and protein levels were measured using quantitative real-time PCR and immunohistochemistry, respectively.

Results

In postmenopausal women, we observed higher levels of phosphorylated IGF-I/insulin receptor (pIGF1R/pIR) in diabetic versus non-diabetic women (p value =0.02), while women who reported regular nonsteroidal anti-inflammatory drug use versus no use had higher levels of insulin and progesterone receptors (both p values ≤0.03). We also noted differences in pIGF1R/pIR staining with OC use (postmenopausal women only), and the proportion of estrogen receptor-positive tissues varied by the number of live births and PTEN status (premenopausal only) (p values ≤0.04). Compared to premenopausal proliferative phase women, postmenopausal women exhibited lower mRNA levels of IGF1, but higher IGFBP1 and IGFBP3 expression (all p values ≤0.004), and higher protein levels of the receptors for estrogen, insulin, and IGF-I (all p values ≤0.02). Conversely, pIGF1R/pIR levels were higher in premenopausal proliferative phase versus postmenopausal endometrium (p value =0.01).

Conclusions

These results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis.
Appendix
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Metadata
Title
Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors
Authors
Melissa A. Merritt
Howard D. Strickler
Mark H. Einstein
Hannah P. Yang
Mark E. Sherman
Nicolas Wentzensen
Jurriaan Brouwer-Visser
Maria Jose Cossio
Kathleen D. Whitney
Herbert Yu
Marc J. Gunter
Gloria S. Huang
Publication date
01-06-2016
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 6/2016
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-016-0751-4

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