Oestrogens in the initiation and promotion of breast cancer

Author(s):  
R. D. Bulbrook ◽  
R. E. Leake ◽  
W. D. George

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.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen Hang ◽  
Shanojie Zhao ◽  
Tiejun Wang ◽  
Yan Zhang

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.


2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Chong Lu ◽  
Xiuhua Wang ◽  
Xiangwang Zhao ◽  
Yue Xin ◽  
Chunping Liu

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.


Cancer ◽  
2020 ◽  
Vol 126 (14) ◽  
pp. 3181-3191 ◽  
Author(s):  
Lauren C. Brown ◽  
Amy R. Murphy ◽  
Chloe S. Lalonde ◽  
Preeti D. Subhedar ◽  
Andrew H. Miller ◽  
...  

2001 ◽  
Vol 35 (5) ◽  
pp. 436-442 ◽  
Author(s):  
Gulnar Azevedo S Mendonça ◽  
José Eluf-Neto

OBJECTIVE: Selecting controls is one of the most difficult tasks in the design of case-control studies. Hospital controls may be inadequate and random controls drawn from the base population may be unavailable. The aim was to assess the use of hospital visitors as controls in a case-control study on the association of organochlorinated compounds and other risk factors for breast cancer conducted in the main hospital of the "Instituto Nacional de Câncer" -- INCA (National Cancer Institute) in Rio de Janeiro (Brazil). METHODS: The study included 177 incident cases and 377 controls recruited among female visitors. Three different models of control group composition were compared: Model 1, with all selected visitors; Model 2, excluding women visiting relatives with breast cancer; and Model 3, excluding all women visiting relatives with any type of cancer. Odds ratios (OR) and 95% confidence intervals were calculated to test the associations. RESULTS: Age-adjusted OR for breast cancer associated with risk factors other than family history of cancer, except smoking and breast size, were similar in the three models. Regarding family history of all cancers, except for breast cancer, there was a decreased risk in Models 1 and 2, while in Model 3 there was an increased risk, but not statistically significant. Family history of breast cancer was a risk factor in Models 2 and 3, but no association was found in Model 1. In multivariate analysis a significant risk of breast cancer was found when there was a family history of breast cancer in Models 2 and 3 but not in Model 1. CONCLUSIONS: These results indicate that while investigating risk factors unrelated to family history of cancer, the use of hospital visitors as controls may be a valid and feasible alternative.


2011 ◽  
Vol 07 (02) ◽  
pp. 116
Author(s):  
Yogesh Gandhi ◽  
Sunil Gandhi ◽  
◽  

An accurate cancer diagnosis is critical as it can direct the use of site-directed, and potentially more effective, treatment options for specific types of cancer. A differential or uncertain diagnosis could prevent cancer patients from receiving optimal treatment, thus affecting their overall prognosis. Advances in molecular technology have led to the development of molecular cancer classifiers that can direct or confirm the diagnosis of metastatic cancers which would otherwise be considered uncertain or unknown. This case report describes the role of molecular diagnostics in the evaluation of a patient with a large pancreatic mass and a history of breast cancer. Results from a 92-gene molecular profiling assay (CancerTYPE ID®) predicted that this new mass was breast cancer. This diagnosis allowed for effective treatment and complete response in this patient.


2021 ◽  
Vol 23 (1) ◽  
pp. 380
Author(s):  
Sebastian Morales-Pison ◽  
Valentina Carrasco ◽  
Cristian Gutiérrez-Vera ◽  
José Miguel Reyes ◽  
Patricio Gonzalez-Hormazabal ◽  
...  

MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C>A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C>A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C>A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.


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