Progesterone receptor isoform identification and subcellular localization in endometrial cancer

被引:49
作者
Leslie, KK
Stein, MP
Kumar, NS
Dai, DH
Stephens, J
Wandinger-Ness, A
Glueck, DH
机构
[1] Univ New Mexico, Dept Obstet & Gynecol, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Hlth Sci Ctr, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA
[3] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA
[4] Univ Colorado, Hlth Sci Ctr, Dept Internal Med, Denver, CO 80220 USA
[5] Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80220 USA
[6] Univ Colorado, Hlth Sci Ctr, Dept Biostat, Denver, CO 80220 USA
关键词
uterus; endometrium; estrogen; progesterone; receptors; human; trafficking;
D O I
10.1016/j.ygyno.2004.09.057
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective. These studies were undertaken to characterize the subcellular localization of the two major isoforms of progesterone receptors (PR), PRA and PRB, in endometrial cancer. Methods. 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. Results. 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). Conclusion. 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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:32 / 41
页数:10
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