GSE108607 SUMOylation Regulates Transcription by the Progesterone Receptor A Isoform in a Target Gene Selective Manner

Contributors : Hany A Abdel-Hafiz ; Kate B HorwitzSeries Type : Expression profiling by arrayOrganism : Homo sapiensLuminal breast cancers express estrogen (ER) and progesterone (PR) receptors, and respond to endocrine therapies. However, some ER+PR+ tumors display intrinsic or acquired resistance, possibly related to PR. Two PR isoforms, PR-A and PR-B, regulate distinct gene subsets that may differentially influence tumor fate. A high PR-A:PR-B ratio is associated with poor prognosis and tamoxifen resistance. We speculate that excessive PR-A marks tumors that will relapse early. Here we address mechanisms by which PR-A regulate transcription, focusing on SUMOylation. We use receptor mutants and synthetic promoter/reporters to show that SUMOylation deficiency or the deSUMOylase SENP1 enhance transcription by PR-A, independent of the receptors ’ dimerization interface or DNA binding domain. De-SUMOylation exposes the agonist properties of the antiprogestin RU486. Thus, on synthetic promoters, SUMOylation functions as an independent brake on transcription by PR-A. What about PR-A SUMOylation of endogenous human breast cancer genes? To st udy these, we used gene expression profiling. Surprisingly, PR-A SUMOylation influences progestin target genes differentially, with some upregulated, others downregulated, and others unaffected. Hormone-independent gene regulation is also PR-A SUMOylation dependent. Several SUMOylated genes were ana lyzed in clinical breast cancer databas...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Related Links:

We examined the influence of decision-making on outcomes of PET failure as a secondary analysis as part of a large observational study.MethodsConsecutive patients treated with PET between 2005 and 2015 for operable breast cancers were included in a retrospective observational study in 3 breast centres in the North-East. Treatment decision processes were examined by case note review and outcomes of treatment success or failure recorded.Results488 patients were included with mean follow-up of 31  months. Overall 63 (12%) experienced treatment failure. 227 (46.6%) were given a choice between surgery and PET at diagnosis....
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Corsi D, Carbognin L, Mazzotta M, Bria E, Foglietta J, Samaritani R, Garufi C, Mariani L, Barni S, Mirabelli R, Sarmiento R, Graziano V, Santini D, Marchetti P, Tonini G, Di Lauro L, Sanguineti G, Paoletti G, Tomao S, De Maria R, Veltri E, Paris I, Giotta F, Latorre A, Giordano A, Ciliberto G, Vici P Abstract We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, lengt...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
Conclusion(s)The results for the overall population and Japanese patients in PALOMA-3 suggest that palbociclib plus fulvestrant was effective and well tolerated in Japanese patients with HR+/HER2 ‒ MBC whose disease had progressed on prior endocrine therapy (Pfizer; NCT01942135).
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsDespite selecting for early-stage breast cancer, racial disparities between White and Black women in time to all forms of breast cancer treatment persist. These disparities while likely not oncologically significant do suggest institutional barriers for obtaining care faced by women of color which may not be addressed with improving access to mammography alone.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Abstract Estrogen receptor(ER)-positive breast cancer accounts for approximately 80%of all breast cancers. The basic concept of endocrine therapy is to deplete estrogen(LH-RH agonist and aromatase inhibitor)and inhibit the action of estrogen against estrogen-dependent growth in ER-positive breast cancer. Recently, new molecular targeting agents, including an mTOR inhibitor and a CDK4/6 inhibitor, have been used in combination with endocrine therapy for the treatment of ER-positive metastatic breast cancer. PMID: 30374008 [PubMed - in process]
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Tags: Clin Calcium Source Type: research
In this study, we review the approaches that have been undertaken to discover these new anti-ERα compounds, especially considering those focused on evaluating ERα degradation. A literature analysis demonstrated that current strategies for discovering new anti-BC drugs are focusing on the identification either of novel ERα inhibitors, of compounds that inhibit ERα-related pathways or of drugs that influence ERα-unrelated cellular pathways. Several lines of evidence suggest that all of these molecules alter the ERα content and block the proliferation of both primary and MBCs. In turn, we p...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
Condition:   Breast Cancer Interventions:   Biological: Pembrolizumab (K);   Drug: Placebo (P);   Drug: Paclitaxel (X);   Drug: Doxorubicin hydrochloride (A);   Drug: Epirubicin (E);   Drug: Cyclophosphamide (C);   Drug: Endocrine therapy;   Radiation: Radiation therapy;   Procedure: Surgery Sponsor:   Merck Sharp & Dohme Corp. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: Breast Cancer | Cancer | Cancer & Oncology | Databases & Libraries | Endocrine Therapy | Genetics | Hormones | Tamoxifen