Regulation of nuclear receptor and cofactor expression in breast cancer cell lines

Abstract

Objective: The aim of this study was to compare the expression profile of nuclear receptors (NRs) and cofactors in different breast cancer cell lines as well as their regulation by estradiol, insulin and progestin R5020. Methods: Expression of NRs and cofactors were determined from MCF-7, T-47D and ZR-75-1 breast cancer cell lines. Multiprobe ribonuclease protection assay and real-time RT-PCR were used to quantitate mRNA levels of steroid receptors, vitamin D receptors (VDR) and retinoic acid receptors (RAR) and cofactors: amplified in breast cancer-1, cyclic AMP response element binding protein (CBP), p300/CBP-associated factor, p300, nuclear receptor corepressor and silencing mediator of repressed transcription. Results: Basal expression levels of NRs and cofactors varied depending on the cell line. Cell line-specific regulation of androgen receptor, estrogen receptor-a (ERa), RARa, RARg and VDR expression was observed after estradiol treatment. Likewise, differences in the regulation of ERa, RARa and VDR expression after R5020 treatment were observed. We did not observe significant regulation of cofactor expression after estradiol, insulin or progestin treatment in any cell line analyzed. Conclusions:The results showed that not only is the expression profile of the NRs and cofactors cell line specific but also the regulation of NR expression. Thus the determinants of the ligand action (receptor and cofactor expression) varied considerably among different cell clones of the breast cancer cells. This suggested a gradient of NR-ligand sensitivities in the hormone-dependent breast cancers, which produces an additional challenge in developing novel ligands for hormone replacement therapy and breast cancer treatment.

Expression of the Forkhead Transcription Factor FOXP1 Is Associated with Estrogen Receptor α and Improved Survival in Primary Human Breast Carcinomas

“…Another alternative is that FOXP1 might act as a coregulator of the ER, the lack of E 2 regulation is consistent with data obtained for other known ER coregulatory molecules whose levels are also unaffected by E 2 (13). Ligand-dependent activation of gene transcription by nuclear receptors such as retinoic acid receptor, thyroid hormone receptor, ER, and peroxisome proliferator-activated receptor ␥ are dependent on the recruitment of coactivators.…”

Changes in expression of steroid receptors, their downstream target genes and their associated co-regulators during the sequential acquisition of tamoxifen resistance in vitro

“…AIB-1 expression correlated with poorer prognosis in breast cancer and reduced response to hormonal therapy (15). Elevated levels of AIB-1 have been reported in other breast cancer cell studies (32,33,44,45). Elevated levels in our in vitro TAMr model strengthen the involvement of AIB-1 in breast carcinogenesis and its further elevation in TAMr suggests it may be contributory to this phenomenon.…”

Estrogenically regulated LRP16 interacts with estrogen receptor α and enhances the receptor’s transcriptional activity

“…Results shown in A and B are representatives of two independent trials. Endocrine-Related Cancer (2007) 14 741-753 www.endocrinology-journals.org of the ERa cofactor expression levels are not hormonally regulated (Misiti et al 1998, Thenot et al 1999, Vienonen et al 2003). Yet, there is evidence that a number of cofactors themselves are regulated by E 2 .…”