Insulin-IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factorsReport as inadecuate

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Cancer Causes and Control

, Volume 27, Issue 6, pp 737–748

First Online: 28 April 2016Received: 16 October 2015Accepted: 16 April 2016DOI: 10.1007-s10552-016-0751-4

Cite this article as: Merritt, M.A., Strickler, H.D., Einstein, M.H. et al. Cancer Causes Control 2016 27: 737. doi:10.1007-s10552-016-0751-4


PurposeExperimental 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.

MethodsWe 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.

ResultsIn 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.

ConclusionsThese results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis.

KeywordsInsulin-like growth factor Insulin Estrogen receptor Endometrium Endometrial cancer Marc J. Gunter and Gloria S. Huang have contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s10552-016-0751-4 contains supplementary material, which is available to authorized users.

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Author: Melissa A. Merritt - Howard D. Strickler - Mark H. Einstein - Hannah P. Yang - Mark E. Sherman - Nicolas Wentzensen - J


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