TY - JOUR
T1 - Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors
AU - Merritt, Melissa A.
AU - Strickler, Howard D.
AU - Einstein, Mark H.
AU - Yang, Hannah P.
AU - Sherman, Mark E.
AU - Wentzensen, Nicolas
AU - Brouwer-Visser, Jurriaan
AU - Cossio, Maria Jose
AU - Whitney, Kathleen D.
AU - Yu, Herbert
AU - Gunter, Marc J.
AU - Huang, Gloria S.
N1 - Funding Information:
This study was funded by the National Institutes of Health National Cancer Institute (Grant Number 1R01CA133010 to M.J.G.), and G.S.H. was supported by the Reproductive Scientist Development Program through the American Congress of Obstetricians and Gynecologists.
Funding Information:
We acknowledge the use of the Albert Einstein Cancer Center Shared Resources (Analytical Imaging Facility, Biorepository and Histopathology) supported by the Cancer Center Support Grant (National Cancer Institute P30 CA013330). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Endometrial cancer
KW - Endometrium
KW - Estrogen receptor
KW - Insulin
KW - Insulin-like growth factor
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U2 - 10.1007/s10552-016-0751-4
DO - 10.1007/s10552-016-0751-4
M3 - Article
C2 - 27125830
AN - SCOPUS:84964412346
SN - 0957-5243
VL - 27
SP - 737
EP - 748
JO - Cancer Causes and Control
JF - Cancer Causes and Control
IS - 6
ER -
