Tamoxifen suppresses expression of prolactin receptor in breast cancer cell lines

Abstract

Breast cancer (BCA) is the most common cancer worldwide in women and a highly heterogeneous disease. Human prolactin receptor (PRLR) is a cell surface receptor regularly presented in cells of mammary gland. It is a single pass transmembrane protein that belong to class I cytokine receptor superfamily. It has been reported that the expression in several types of cancer, especially BCA. Tamoxifen is a non-steroidal anti-estrogenic drug which considered for hormone therapy with minimal adverse effects via blocking of estrogen function in BCA cells by competitive binding to estrogen receptor (ER). Previous study has been reported for the decreasing PRLR mRNA expression level after treatment with tamoxifen in BCA patients. However, this finding had not been confirmed the protein expression level by in vitro experiment. This study aimed to investigate the effect of tamoxifen in PRLR expression at protein level on BCA cell lines. The expression of PRLR in BCA cell lines including T47D, MCF-7, MDA-MB-231, HCC70, BCA55-121, PC-B-120CA and PC-B-142CA were observed by immunofluorescence analysis (IFA) and western blot analysis and further observed the localization by confocal microscopy analysis. The treatment of tamoxifen on BCA cells and detection of PRLR protein expression was performed. Only T47D, MCF-7, HCC70 and PC-B-142CA cells showed PRLR expression by both IFA and western blot. Western blot results also showed different isoforms of PRLR expression on each BCA cell line. Confocal microscopy analysis determined high membrane expression in T47D cells while only cytoplasmic expression in MCF-7, HCC70 and PC-B-142CA cells. Treatment with tamoxifen showed down-regulation of PRLR in T47D and MCF-7 cells while HCC70 did not change. In conclusion, tamoxifen showed the effect to down-regulate PRLR protein expression in BCA cell lines, confirmed previous finding in BCA patients. This may indicate the other consideration of using tamoxifen in therapeutic approach of BCA patients.