Deregulation of estrogen receptor coactivator proline-, glutamic acid-, and leucine-rich protein-1/modulator of nongenomic activity of estrogen receptor in human endometrial tumors

Ratna K. Vadlamudi, Seetharaman Balasenthil, Russell R. Broaddus, Jan Åke Gustafsson, Rakesh Kumar

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Proline-, glutamic acid-, and leucine-rich protein-1)PELP1/ MNAR [modulator of nongenomic activity of estrogen receptor (ER)], a novel coregulatory protein, modulates genomic as well as nongenomic activity of ERs. We characterized the expression and localization of PELP1 in both benign and cancerous endometrium. Our results suggest that PELP1 is expressed in all stages of endometrium; however, this protein exhibits distinct localization depending on the phase. PELP1 is expressed in both the stroma and epithelial cells. Using the Ishikawa endometrial cancer model cell line and ER subtype-specific ligands, we found that PELP1 functionally interacts with both ERα and ERβ and enhances their transcriptional responses. However, in endometrial cancer cells, endogenous PELP1 is also required for optimal ligand-mediated transcription and proliferation responses. PELP1 promoted a tamoxifen-mediated agonistic action in endometrial, but not in breast cancer cells. PELP1 expression and localization are widely deregulated in endometrial cancers. In addition, PELP1 and ERβ were localized predominantly in the cytoplasm of high-grade endometrial tumors. Our results suggest that PELP1 plays an essential role in the proliferation of cancerous endometrial cells.

Original languageEnglish (US)
Pages (from-to)6130-6138
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number12
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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