scholarly journals Retrospective analysis of estrogen receptor�1 and N‑acetyltransferase gene expression in normal breast tissue, primary breast tumors, and established breast cancer cell lines

Author(s):  
Samantha Carlisle ◽  
David Hein
2012 ◽  
Vol 21 (11 Supplement) ◽  
pp. 71-71
Author(s):  
Xuezheng Sun ◽  
Gretchen L. Gierach ◽  
Rupninder Sandhu ◽  
Tyisha Williams ◽  
Norman Boyd ◽  
...  

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S39384 ◽  
Author(s):  
David N. Danforth

Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women.


2020 ◽  
Author(s):  
Nabila Kazmi ◽  
Tim Robinson ◽  
Jie Zheng ◽  
Siddhartha Kar ◽  
Richard M Martin ◽  
...  

AbstractBackgroundRho GTPases are a family of 20 intracellular signalling proteins that influence cytoskeletal dynamics, cell migration and cell cycle progression. Rho GTPases are implicated in breast cancer progression but their role in breast cancer aetiology is unknown. As aberrant Rho GTPase activity could be associated with breast cancer, we aimed to determine the potential for a causal role of Rho GTPase gene expression in breast cancer risk, using two-sample Mendelian randomization (MR).MethodsMR was undertaken in 122,977 breast cancer cases and 105,974 controls, including 69,501 estrogen receptor positive (ER+) cases and 105,974 controls, and 21,468 ER negative (ER-) cases and 105,974 controls. Single nucleotide polymorphisms (SNPs) underlying expression quantitative trait loci (eQTLs) obtained from normal breast tissue, breast cancer tissue and blood were used as genetic instruments for Rho GTPase expression. Colocalisation was performed as a sensitivity analysis to examine whether findings reflected shared causal variants or genomic confounding.ResultsWe identified genetic instruments for 14 of the 20 human Rho GTPases. Using eQTLs obtained from normal breast tissue and normal blood, we identified evidence of a causal role of RHOD in overall and ER+ breast cancers (overall breast cancer: odds ratio (OR) per standard deviation (SD) increase in expression level 1.06; (95% confidence interval (CI): 1.03, 1.09; P=5.65×10-5) and OR 1.22 (95% CI: 1.11, 1.35; P=5.22×10−5) in normal breast tissue and blood respectively). The direction of association was consistent for ER- breast cancer, although the effect-estimate was imprecisely estimated. Using eQTLs from breast cancer tissue and normal blood there was some evidence that CDC42 was inversely associated with overall and ER+ breast cancer risk. The evidence from colocalization analyses strongly supported the MR results particularly for RHOD.ConclusionsOur study suggests a potential causal role of increased RHOD gene expression, and a potential protective role for CDC42 gene expression, in overall and ER+ breast cancers. These finding warrant validation in independent samples and further biological investigation to assess whether they may be suitable targets for drug targeting.


2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Hannah Oh ◽  
A Heather Eliassen ◽  
Molin Wang ◽  
Stephanie A Smith-Warner ◽  
Andrew H Beck ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20057-20057
Author(s):  
C. Schem ◽  
A. M. Stark ◽  
H. M. Mehdorn ◽  
W. Jonat ◽  
N. Maass

20057 Background: Recently our demonstrated that the expression of several Metastasis Suppressor Genes (MSG) is reduced in breast cancer brain metastases. Current data suggest that MSG Maspin (serpin B5) is a promising candidate for further treatment options. So, we examined the mRNA and protein expression of Maspin in normal breast tissue, breast cancer primaries, -brain metastases and breast cancer cell lines. Methods: Maspin mRNA expression was examined by real time reverse transcription polymerase chain reaction (RT-PCR) in fresh frozen samples from normal breast tissue, breast cancer primaries and -brain metastases. Furthermore maspin was examined in poorly invasive and non-metastatic breast cancer cell lines MCF-7, T47-D, in highly invasive and metastatic MDA-MB-231 breast cancer cells (231-parental) and in brain- and bone-selective metastatic clones (231-brain, 231-bone). Maspin protein was detected by immunohistochemistry in paraffin-embedded sections from 16 patients with breast cancer primaries and brain metastases using a specific monoclonal mouse antibody. Results: In relation to normal breast tissue, maspin mRNA expression was decreased in primary tumors and again decreased in brain metastases. Normalized ΔCT values were 1 (normal tissue), 0.3 (primary tumors) and 0.13 (brain metastases). Immunohistochemistry revealed the same tendency. 3 of 16 (19%) breast cancer primaries were positive whereas none of the brain metastases showed positive maspin staining. In comparison to poorly invasive breast cancer cell lines, maspin mRNA expression was decreased in 231-parental, increased in 231-brain and not detectable in 231-bone. Conclusions: Maspin expression is reduced in breast cancer brain metastases. It is differentially expressed in brain- and bone-selective metastatic cell lines. These results suggest an important role for maspin in breast cancer brain metastasis. No significant financial relationships to disclose.


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