Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes

Daniel, Andrea R.; Gaviglio, Angela L.; Knutson, Todd P.; Ostrander, Julie H.; D’Assoro, Antonino B.; Ravindranathan, Preethi; Peng, Yan; Raj, Ganesh V.; Yee, Douglas

doi:10.1038/onc.2013.579

Cited by 118 publications

(137 citation statements)

References 48 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…The master regulator of progesterone response in breast cancer appears to be estrogen dependent which regulates PR abundance, thereby permitting PR-DNA binding, which suggests that the action of estrogen and progesterone is inextricably linked. ER and PR have the longest co-existence in relation to other receptors such that ERa-mediated up-regulation of PR abundance permits activity in response to progesterone, and PR in turn regulates a subset of ERa actions [28,37,38].…”

Section: Discussionmentioning

confidence: 99%

Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells

et al. 2016

View full text Add to dashboard Cite

Steroid hormones and their nuclear receptors play a major role in the development and progression of breast cancer. MCF-7 cells are triple-positive breast cancer cells expressing estrogen receptor (ER), progesterone receptor (PR), and glucocorticoid receptor (GR). However, interaction and their role in expression pattern of activator protein (AP-1) transcription factors (TFs) are not completely understood. Hence, in our study, MCF-7 cells were used as an in vitro model system to study the interplay between the receptors and hormones. MCF-7 cells were treated with estradiol-17b (E2), progesterone (P4), and dexamethasone (Dex), alone or in combination, to study the proliferation of cells and expression of AP-1 genes. MTT assay results show that E2 or P4 induced the cell proliferation by more than 35 %, and Dex decreased the proliferation by 26 %. E2 and P4 are found to increase ERa by more than twofold and c-Jun, c-Fos, and Fra-1 AP-1 TFs by more than 1.7-fold, while Dex shows opposite effect of E2-or P4-induced effect as well as effect on the expression of nuclear receptors and AP-1 factors. E2 antagonist Fulvestrant (ICI 182,780) found to reduce proliferation and E2-induced expression of AP1-TFs, while P4 or Dex antagonist Mifepristone (RU486) is found to block GRmediated expression of NRs and AP-1 mRNAs. Results suggest that E2 and P4 act synergistically, and Dex acts as an antagonist of E2 and P4.

show abstract

Section: Discussionmentioning

confidence: 99%

Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In the presence of both estrogen and progesterone, PGR was shown to be recruited to the ESR1 complex and to redirect ESR1-binding events, resulting in a gene expression profile associated with better clinical outcome (Mohammed et al 2015). However, in the presence of estrogen alone, un-liganded PGRB activated a subset of ER target genes by acting as a molecular scaffold for the formation of a transcriptional complex with ESR1 and PELP1, resulting in a more aggressive proliferative response to estrogen (Daniel et al 2015). It is likely that the action of ESR1 and PGR and their crosstalk are highly context dependent.…”

Section: Combinatorial Control Of Gene Expression By Nrs In Breast Camentioning

confidence: 99%

Emerging functional roles of nuclear receptors in breast cancer

Doan

Graham

2017

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Nuclear receptors (NRs) have been targets of intensive drug development for decades due to their roles as key regulators of multiple developmental, physiological and disease processes. In breast cancer, expression of the estrogen and progesterone receptor remains clinically important in predicting prognosis and determining therapeutic strategies. More recently, there is growing evidence supporting the involvement of multiple nuclear receptors other than the estrogen and progesterone receptors, in the regulation of various processes important to the initiation and progression of breast cancer. We review new insights into the mechanisms of action of NRs made possible by recent advances in genomic technologies and focus on the emerging functional roles of NRs in breast cancer biology, including their involvement in circadian regulation, metabolic reprogramming and breast cancer migration and metastasis.

show abstract

“…[68][69][70] In 2015, researchers 67 conducted a comparative study by IHC on the sensitivity of PELP1, compared with GATA3, in TNBC tissues. They found that, of the 70 TNBC tumors, 67 (96%) showed strong, diffuse nuclear staining for PELP1, whereas only 46% (32 of 69) of the tumors were positive for GATA3 (the tissue from one case did not survive processing) (P , .001).…”

Section: Diagnostic Utility Of Gata3 In Tnbcsmentioning

confidence: 99%

Update on Immunohistochemical Analysis in Breast Lesions

Peng¹,

Butt²,

Chen³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.-The utility of immunohistochemistry (IHC) in breast lesions needs to be updated with exceptions among these lesions. Biomarker studies with IHC in triple-negative breast carcinoma may help develop targeted therapies for this aggressive breast cancer. The distinction of metastatic lung adenocarcinoma to the breast and invasive breast carcinoma has significant prognostic and therapeutic implications. The determination can be challenging because both primary tumors can express estrogen receptor and/or HER2 by IHC, creating a diagnostic dilemma.Objectives.-To provide a practical update on the use of IHC markers in differential diagnoses in breast lesions, including benign, atypical, precancerous, and malignant tumors; to highlight recently published research findings on novel IHC markers in triple-negative breast carcinoma cases; and to reinforce the importance of IHC use as an ancillary tool in distinguishing metastatic lung adenocarcinoma to the breast from primary breast carcinoma using real case examples.Data Sources.-PubMed (US National Library of Medicine, Bethesda, Maryland) literature review and authors' research data and personal experiences were used in this review.Conclusions.-Immunohistochemistry has an important role in making differential diagnoses in breast lesions in morphologically equivocal settings; recognizing IHC expression status in the exceptions among these lesions will aid in the correct diagnosis of challenging breast cases. Studies suggest that androgen receptor, p16, p53, GATA3, and PELP1 may have potential diagnostic, prognostic, and predictive value in triple-negative breast carcinoma cases; these findings may provide insight and a greater understanding of the tumor biology in triple-negative breast carcinomas. In distinguishing metastatic estrogen receptor-positive or HER2 þ lung adenocarcinoma to the breast from primary breast carcinoma, napsin A, TTF-1, and GATA3 comprise a useful IHC panel.

show abstract

Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes

Cited by 118 publications

References 48 publications

Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells

Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells

Emerging functional roles of nuclear receptors in breast cancer

Update on Immunohistochemical Analysis in Breast Lesions

Contact Info

Product

Resources

About