Progesterone receptor isoform identification and subcellular localization in endometrial cancer

Kimberly K Leslie; Mary-Pat Stein; Nirmala S Kumar; Donghai Dai; Janet Stephens; Angela Wandinger-Ness; Deborah H Glueck

doi:10.1016/j.ygyno.2004.09.057

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Progesterone receptor isoform identification and subcellular localization in endometrial cancer

Journal article

Peer reviewed

Progesterone receptor isoform identification and subcellular localization in endometrial cancer

Kimberly K Leslie, Mary-Pat Stein, Nirmala S Kumar, Donghai Dai, Janet Stephens, Angela Wandinger-Ness and Deborah H Glueck

Gynecologic oncology, Vol.96(1), pp.32-41

2005

DOI: 10.1016/j.ygyno.2004.09.057

PMCID: PMC2755492

PMID: 15589577

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Abstract

These studies were undertaken to characterize the subcellular localization of the two major isoforms of progesterone receptors (PR), PRA and PRB, in endometrial cancer. Immunohistochemistry, immunoprecipitation, and confocal microscopy were performed using Hec50co and KLE endometrial cancer cell models expressing PRA or PRB as a consequence of transduction. The location of PRB compared to PRA was determined, and antibodies were tested for specificity with respect to PR isoform recognition. Immunohistochemical analyses of PR expression and subcellular compartmentalization were also performed on 20 formalin-fixed endometrial cancer tumors. Morphological and biochemical evaluations demonstrated that PRA is localized to the nucleus, even in the absence of progesterone. In contrast, a large proportion of PRB is cytoplasmic in the absence of ligand, but is rapidly translocated to the nucleus in the presence of progesterone. The differential distribution of PRA and PRB proved to be a hallmark of malignant and nonmalignant epithelia in 20 samples of archival endometrial tissue from women with the pre-operative diagnosis of endometrial cancer. All endometrial cancer specimens demonstrated cytoplasmic PRB in 50% or more of the cells, and five of the seven tumors that were moderately to poorly differentiated demonstrated no PRB staining in the nuclei. Nuclear PRB was significantly associated with increasing tumor differentiation ( P = 0.031). In the absence of ligand, PRA is nuclear and PRB is largely cytoplasmic. This suggests that PRA may exert ligand-independent nuclear effects, while PRB may have nongenomic cytoplasmic actions in endometrial cancer cells.

Receptors

Endometrium

Estrogen

Human

Progesterone

Trafficking

Uterus

Details

Title: Subtitle: Progesterone receptor isoform identification and subcellular localization in endometrial cancer
Creators: Kimberly K Leslie - University of Iowa, Obstetrics and Gynecology
Mary-Pat Stein - Department of Pathology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Nirmala S Kumar - Department of Internal Medicine, The University of Colorado Health Sciences Center, Denver, CO 80220, USA
Donghai Dai - University of Iowa, Obstetrics and Gynecology
Janet Stephens - Department of Pathology, The University of Colorado Health Sciences Center, Denver, CO 80220, USA
Angela Wandinger-Ness - Department of Pathology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Deborah H Glueck - Department of Biostatistics, The University of Colorado Health Sciences Center, Denver, CO 80220, USA
Resource Type: Journal article
Publication Details: Gynecologic oncology, Vol.96(1), pp.32-41
DOI: 10.1016/j.ygyno.2004.09.057
PMID: 15589577
PMCID: PMC2755492
NLM abbreviation: Gynecol Oncol
ISSN: 0090-8258
eISSN: 1095-6859
Publisher: Elsevier Inc
Language: English
Date published: 2005
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983557450902771

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