Deregulation of estrogen receptor coactivator proline-, glutamic acid-, and leucine-rich protein-1/modulator of nongenomic activity of estrogen receptor in human endometrial tumors.
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 ERalpha and ERbeta 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 ERbeta 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.
Vadlamudi
Ratna K
RK
Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, USA. rvadla@LSUHSC.edu
Balasenthil
Seetharaman
S
Broaddus
Russell R
RR
Gustafsson
Jan-Ake
JA
Kumar
Rakesh
R
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002455:Cell Division; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D017154:Stromal Cells / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
D018931:Antineoplastic Agents, Hormonal; D056970:Co-Repressor Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C438485:PELP1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D013629:Tamoxifen