Mutual regulations and breast cancer cell control by steroidogenic enzymes: dual sex-hormone receptor modulation upon 17β-HSD7 inhibition

In this study, MCF-7 and T47D cells were treated with inhibitors of 17β-HSD1, 17β-HSD7, aromatase or steroid sulfatase (STS), then mRNA levels of 17β-HSD7, STS, 11β-HSD 2, estrogen receptors α (ERα) and androgen receptor (AR) were determined by Q-PCR. ER negative cell line MDA-MB-231 was used as a negative control. Our results demonstrate that 17β-HSD7, STS and 11β-HSD2 are all regulated by the same estrogen estradiol via ERα. When the gene of ERα (ESR1) was knocked down, there was no longer significant mutual regulation of these enzymes.Our results demonstrate that important steroidogenic enzymes transcriptionally regulated by ERα, can be mutually closely correlated. Inhibition of one of them can reduce the expression of another, thereby amplifying the role of the inhibition. Furthermore, inhibition of 17β-HSD7 increases the expression of AR gene which is considered as a marker for better prognosis in ER + breast cancer, while maintaining ERα level. Thus, our mechanistic finding provides a base for further improving the endocrine therapy of ER + breast cancer, e.g., for selecting the target steroid enzymes, and for the combined targeting of human 17β-HSD7 and ERα.Graphical abstract
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research

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In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors.
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research
Condition:   Breast Neoplasms Intervention:   Drug: Endocrine therapy Sponsor:   Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Current evidence suggests that patients with Luminal A early breast cancer can skip chemotherapy or extended endocrine therapy, but immunohistochemistry-based biomarker analysis for St Gallen subtyping may not...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
Publication date: Available online 13 July 2019Source: Seminars in Cancer BiologyAuthor(s): Zoi Piperigkou, Nikos K. KaramanosAbstractThe biological functions of estrogens are regulated by estrogen receptors (ERα and ERβ), which contribute in the progression of several hormone-responsive cancer types via estrogen signaling mechanisms. The coordinated actions of ERs and extracellular matrix (ECM) macromolecules are principal mediators of ECM remodeling in the tumor and the adjacent stroma. In breast cancer, ERs are critical biomarkers as their expression in breast tumor determines the disease-free survival, yet g...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Fulvestrant 500 mg is an effective and safe treatment for patients with advanced or recurrent breast cancer after prior endocrine treatment. PMID: 31292328 [PubMed - in process]
Source: Journal of Nippon Medical School - Category: Universities & Medical Training Authors: Tags: J Nippon Med Sch Source Type: research
Background Limited evidence exists on the impact of adding a taxane, using endocrine therapy and carrying a deleterious germline BRCA mutation on ovarian reserve measured by anti-müllerian hormone (AMH) levels of young breast cancer patients receiving (neo)adjuvant cyclophosphamide- and anthracycline-based chemotherapy. Methods This is a biomarker analysis including young (≤40 years) early breast cancer patients with known germline BRCA mutational status and available prospectively collected frozen plasma samples before and after chemotherapy. Chemotherapy consisted of either six cycles of FEC (5 fluorouracil ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion: The RSS is comparable to the AJCC8 PS for a patient population receiving chemotherapy as well as endocrine- and HER2-targeted therapy and further stratifies stage IV patients. PMID: 31281728 [PubMed]
Source: Journal of Breast Cancer - Category: Cancer & Oncology Tags: J Breast Cancer Source Type: research
AbstractPurposeApproximately 30% oestrogen receptor alpha (ER α)-positive breast cancer (BC) patients exhibit intrinsic or recurrent resistance to adjuvant endocrine therapy with tamoxifen. The androgen receptor (AR) is expressed in about 90% of ERα-positive patients, with particularly high expression in tamoxifen-resistant tumours. Prostate-derived Ets fact or (PDEF), which is a co-regulator of AR, plays a role in tamoxifen resistance in ERα-positive BC. The purpose of this research was to analyse the potential roles of AR, PDEF and ERα levels in the response to tamoxifen resistance in ERα-po...
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
ConclusionWith [18F]fluoride PET/CT, some first-order features, including those that take into account lesion volume but also some heterogeneity parameters, provide incremental value over SUVmax in predicting clinical response and survival in breast cancer patients with bone metastases treated with endocrine therapy. With [18F]FDG PET/CT, no first-order parameters were more accurate than SUVmax although TLM and skewness were associated with OS and PFS, respectively. Intra-patient heterogeneity of response occurs commonly between metastases with both tracers and most parameters.
Source: Molecular Imaging and Biology - Category: Molecular Biology Source Type: research
Purpose: Lumpectomy (L) and breast radiotherapy (RT) results in equivalent outcomes in comparison to mastectomy (M) for early-stage breast cancer (BC) based on randomized controlled trials (RCT). Since 2004, RCT support that L without RT yields equivalent survival and acceptable local-regional outcomes in women ≥70-years old with T1N0 hormone-sensitive (ER+) BC on endocrine therapy. Based on this, we hypothesized that M rates should decrease substantially after 2004 in this low-risk elderly population. Methods: We used the Surveillance Epidemiology and End Results registry data to conduct this study. We included wom...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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