Novel estrogen receptor coactivator PELP1/MNAR gene and ERbeta expression in salivary duct adenocarcinoma: potential therapeutic targets.
Salivary duct carcinoma (SDC) is a high-grade neoplasm with marked morphological resemblance to mammary duct carcinoma. The novel estrogen receptor (ER)-interacting protein and the proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), also called the modulator of nongenomic activity of ER ( MNAR ), have been shown to activate steroid hormone receptors in mammary carcinomas by nongenomic and genomic mechanisms. The expression and the relationship of this gene to the ER status in SDCs are unknown. We investigated the differential expression of the PELP1 / MNAR and the ERs alpha and beta proteins in SDCs, using Western blotting and immunohistochemistry. Western blot analysis of 7 paired normal and tumor specimens showed increased expression of PELP1 / MNAR and ER beta in 3 and 4 of the SDCs, respectively. No detectable expression of ER alpha in any normal or SDC specimens was noted. Immunohistochemical staining performed on 70 SDCs revealed strong expression of PELP1 / MNAR in 51 (73%) and ER beta in 52 (74%) tumors. PELP1 / MNAR and ER beta were coexpressed in 35 (50%), individually in 17 (24.2%), and negative in 18 (25.7%) tumors. PELP1 / MNAR staining was predominantly cytoplasmic whereas ER beta staining was nuclear and occasionally cytoplasmic in tumor cells. Our results indicate that PELP1 / MNAR and ER beta are coexpressed in most SDCs and may play a role in the pathobiology of these tumors.
Vadlamudi
Ratna K
RK
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Balasenthil
Seetharaman
S
Sahin
Aysegul A
AA
Kies
Merrill
M
Weber
Randal S
RS
Kumar
Rakesh
R
El-Naggar
Adel K
AK
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D056970:Co-Repressor Proteins; D047629:Estrogen Receptor beta / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012468:Salivary Gland Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors
D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; D047629:Estrogen Receptor beta; C438485:PELP1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors