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Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression

Oncogene volume 20, pages 6965–6969 (2001)Cite this article

Abstract

Both the estrogen receptor (ER) and the progesterone receptor (PR) have two subtypes: ER-α and β, and PR-A and -B, respectively. These subtypes differ in function and expression, and recent reports have correlated changes in the normal proportions of these isoforms with neoplastic states. We investigated ER and PR isoform expression in normal pre- and post-menopausal endometrium, well-differentiated endometrial adenocarcinoma, and poorly differentiated malignant mixed mullerian tumors (MMMTs). Semi-quantitative RT–PCR and immunoblotting were used to measure receptor mRNA and protein expression. Estrogen receptor-α/β mRNA ratios were significantly higher in postmenopausal (27.3) compared to premenopausal endometrium (4.9) mainly as a result of lower ER-β expression in the former. Compared to age-matched postmenopausal controls, the ER-α/β ratio was reduced in both grade I adenocarcinoma and MMMT specimens (3.3 and 6.8, respectively), due to a selective loss of ER-α. The relative abundance of PR-A and PR-B mRNA remained unchanged between all tissue subtypes. Total PR protein, however, was significantly reduced in MMMTs compared to all other groups. Thus, sex steroid receptor expression is significantly and differentially altered in well-differentiated and poorly-differentiated endometrial cancers. Both cancers exhibit decreased ER-α expression and the MMMTs also demonstrate a significant loss of PR protein.

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Acknowledgements

Supported by a grant from the National Institutes of Health K08 CA73668-01 to LW Rice, National Institutes of Health R01 DK57082 to MA Shupnik, and by the Molecular Core and Project 2 to MA Shupnik of the Center for Research in Reproduction at the University of Virginia through cooperative agreement as part of the Specialized Cooperative Centers Program in Reproduction Research NICHD/NIH U54 HD 28934.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Health Sciences Center, Charlottesville, VA 22906, Virginia, USA

    Amir A Jazaeri, Ken J Nunes, M Susan Dalton & Laurel W Rice

  2. Division of Endocrinology, Internal Medicine, University of Virginia, Health Sciences Center, Charlottesville, VA 22906, Virginia, USA

    Miaohou Xu & Margaret A Shupnik

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  1. Amir A Jazaeri
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  2. Ken J Nunes
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Correspondence to Laurel W Rice.

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Jazaeri, A., Nunes, K., Dalton, M. et al. Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered ER and PR isoform expression. Oncogene 20, 6965–6969 (2001). https://doi.org/10.1038/sj.onc.1204809

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