scholarly journals Endogenous estrogens—breast cancer and chemoprevention

2021 ◽  
Author(s):  
Beata Starek-Świechowicz ◽  
Bogusława Budziszewska ◽  
Andrzej Starek
Keyword(s):  
Breast Cancer ◽  
Estrogen Metabolism ◽  
Oxygen Species ◽  
Breast Malignancy ◽  
Proliferation And Differentiation ◽  
17Β Estradiol ◽  
Estrogen Carcinogenesis ◽  
Breast Tissues ◽  
Epigenetic Processes

AbstractBreast cancer is the most common female malignancy and the second leading cause of cancer related deaths. It is estimated that about 40% of all cancer in women is hormonally mediated. Both estrogens and androgens play critical roles in the initiation and development of breast cancer. Estrogens influence normal physiological growth, proliferation, and differentiation of breast tissues, as well as the development and progression of breast malignancy. Breast cancer is caused by numerous endo- and exogenous risk factors. The paper presents estrogen metabolism, in particular 17β-estradiol and related hormones. The mechanisms of estrogen carcinogenesis include the participation of estrogen receptors, the genotoxic effect of the estrogen metabolites, and epigenetic processes that are also presented. The role of reactive oxygen species in breast cancer has been described. It called attention to a role of numerous signaling pathways in neoplastic transformation. Chemoprotective agents, besides other phytoestrogens, classical antioxidants, synthetic compounds, and their mechanisms of action have been shown.

scholarly journals Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen Hang ◽  
Shanojie Zhao ◽  
Tiejun Wang ◽  
Yan Zhang
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Nuclear Accumulation ◽  
Migration And Invasion ◽  
Ubiquitin Protein Ligase ◽  
Novel Target ◽  
First Time ◽  
Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

scholarly journals Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Chong Lu ◽  
Xiuhua Wang ◽  
Xiangwang Zhao ◽  
Yue Xin ◽  
Chunping Liu
Keyword(s):  
Breast Cancer ◽  
Normal Breast ◽  
Tumor Promoter ◽  
Women Health ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Migration ◽  
Breast Tissues ◽  
Long Non Coding Rna

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

scholarly journals Tamoxifen protects breast cancer patients from COVID-19: first evidence from real world data

2021 ◽  
Author(s):  
Sara Bravaccini ◽  
Fabio Nicolini ◽  
William Balzi ◽  
Irene Azzali ◽  
Arianna Calistri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Protective Role ◽  
In Vitro Experiments ◽  
Breast Cancer Patients ◽  
Real World Data ◽  
17Β Estradiol ◽  
Hormonal Therapies

Abstract Background COVID-19 severity is uneven between genders. We hypothesized a role of hormonal therapies in the severity of COVID-19 in breast cancer (BC) patients via the modulation of SARS-CoV-2 susceptibility genes. Patients and Methods We mined the Emilia Romagna region (Italy) registries to compare the rates of hospitalization and mortality for COVID-19 in 2020 amongst 24628 BC patients. Next, we analyzed the modulation of ACE2, TMPRSS2 and NRP1 gene expression and the susceptibility to SARS-CoV-2 infection by tamoxifen, fulvestrant and 17β-estradiol on human ER+ MCF-7 cells in vitro.Results The hospitalization rate observed for 4784 tamoxifen treated BC patients was the lowest (OR, 0.41; 95% CI, 0.18-0.94; p=0.04) among hormonal therapies and no fatalities occurred. A standard mortality rate reduction has been observed also for patients treated with aromatase inhibitors (SMR: 0.73; 95% CI, 0.45-0.90). In vitro experiments showed that fulvestrant, but not tamoxifen, increases ACE2, TMPRSS2 and NRP1 gene expression and susceptibility to SARS-CoV-2 infection and that 17β-estradiol reduces significantly TMPRSS2 and NRP1 expression.Conclusions Tamoxifen treated BC patients showed a reduced rate of hospitalization and strikingly no fatalities for COVID-19. In vitro experiments confirmed a protective role of tamoxifen while an increased susceptibility to SARS-CoV-2 infection of ER+ cells treated with fulvestrant was observed.

scholarly journals The Role of Hydrogen Peroxide and Other Reactive Oxygen Species in Wound Healing

2011 ◽  
Vol 54 (3) ◽  
pp. 97-101 ◽  
Author(s):  
Jiří Kanta
Keyword(s):  
Reactive Oxygen Species ◽  
Wound Healing ◽  
Reactive Oxygen ◽  
Acute Injury ◽  
Oxygen Species ◽  
Extracellular Matrix Components ◽  
Proliferation And Differentiation ◽  
High Concentrations ◽  
Massive Cell

Wound healing is a complex physiological process important for tissue homeostasis. An acute injury initiates massive cell migration, proliferation and differentiation, synthesis of extracellular matrix components, scar formation and remodelling. Blood flow and tissue oxygenation are parts of the complex regulation of healing. Higher organisms utilize molecular oxygen as a terminal oxidant. This way of gaining energy for vital processes such as healing leads to the production of a number of oxygen compounds that may have a defensive or informatory role. They may be harmful when present in high concentrations. Both the lack and the excess of reactive oxygen species may influence healing negatively.

Oestrogens in the initiation and promotion of breast cancer

1989 ◽  
Vol 95 ◽  
pp. 67-76
Author(s):  
R. D. Bulbrook ◽  
R. E. Leake ◽  
W. D. George
Keyword(s):  
Breast Cancer ◽  
Racial Differences ◽  
Clonal Selection ◽  
Urinary Metabolites ◽  
Endocrine Function ◽  
Case Control Studies ◽  
History Of ◽  
Breast Tissues ◽  
Doubling Times

SynopsisA wide variety of methods has been used to investigate the role of the oestrogens in the aetiology and clinical course of breast cancer. They include measurements of urinary metabolites and the concentrations of oestrogens in blood, saliva, nipple aspirates, cyst fluids, lymph and breast tissues. The function of the oestrogen-binding proteins has also been examined. There is no clear evidence that an excessive oestrogenic stimulus is a determinant of risk of breast cancer and it may be sensible to question this widely-held belief. Variation in the oestrogenic stimulus within the normal range might be responsible for the observed differences in tumour doubling times and for clonal selection. Case/control studies which do not include some measure of tumour growth rates are not an efficient way of investigating these possibilities. Endogenous androgen concentrations show such a strong correlation with the natural history of the disease that it would seem unwise to investigate the role of the oestrogens without taking the androgens into account. Geographical variation in the incidence of breast cancer is probably not due to racial differences in endocrine function.

Dual Aromatase-Sulphatase Inhibitors (DASIs) for the Treatment of Hormone Dependent Breast Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Laxmi Banjare ◽  
Akhlesh Kumar Jain ◽  
Suresh Thareja
Keyword(s):  
Breast Cancer ◽  
Dehydroepiandrosterone Sulfate ◽  
Develop Breast Cancer ◽  
Estrone Sulfate ◽  
Cancer Tissues ◽  
Breast Cancer Inhibition ◽  
Estrogen Biosynthesis ◽  
Breast Tissues ◽  
Cancer Inhibition

: Breast cancer is the most frequent diagnosed cancer in women and the second most common form of cancer, causing death after lung cancer, all across the globe at an alarming rate. The level of estrogens, in breast cancer tissues of postmenopausal women is 10-40 folds higher than the non-carcinogenic breast tissues. As a result of this greater level of estrogen, breast tissue becomes more prone to develop breast cancer; mainly estradiol plays a significant role in the initiation and development of hormone dependent breast cancer. Androstenedione, Adrenal dehydroepiandrosterone sulfate and estrone-sulfate also plays an important role of precursor for estrogen biosynthesis. Estrogens deprivation exhibits an attractive phenomena in the advancement of most ideal therapeutics for the treatment of breast cancer. Inhibition of aromatase and sulphatase emerged as attractive therapy for the treatment of hormone dependent breast cancer via deprivation of estrogen by different pathways. The cocktail of aromatase and sulphatase inhibitors known as dual aromatase-sulphatase inhibitors (DASIs) emerged as an attractive approach for the effective estrogen deprivation. The present review article focused on the journey of dual aromatase-sulphatase inhibitors from the beginning to till date (2020). Keeping in view the key observations, this review may be helpful for medicinal chemists to design and develop new and efficient dual aromatase-sulphatase inhibitors for the possible treatment of hormone-related breast cancer.

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