Journal article
Breast cancer sub-types display heterogeneity in gene amplification and mRNA expression of the anti-apoptotic members of BCL2 family
Gene, Vol.857, pp.147179-147179
03/20/2023
DOI: 10.1016/j.gene.2023.147179
PMID: 36627096
Abstract
•Breast cancers display no alterations in anti-apoptotic BCL2 family members, besides amplifications in MCL1, which is more prevalent in basal cancers.•Subtypes of breast cancer are heterogeneous regarding the expression and reliance on antiapoptotic BCL2 proteins.•Levels of mRNA expression of anti-apoptotic family proteins do not significantly affect survival in breast cancer.
Progress in therapies and improved outcomes in recent decades have followed a better understanding of breast cancers pathogenesis and their heterogeneity but new treatments are needed especially for metastatic disease which remains incurable. Inhibition of apoptosis is a hallmark characteristic of cancer and can be targeted for therapy.
The five anti-apoptotic members of the BCL2 family are at the core of apoptosis execution and are involved in apoptosis evasion of transformed cells. Genetic lesions as well as mRNA regulation of these members in breast cancer and its sub-types and implications for survival outcomes were investigated using data from various publicly available databases.
Genes encoding for anti-apoptotic BCL2 proteins are rarely mutated in breast cancer and copy number alterations are observed only in MCL1 gene which is amplified in a minority of breast cancer ranging from 1.6% to 18.7% in breast cancers. Over-expression of BCL2, BCL-X and MCL1 is observed in luminal A cancers, while cases of luminal B and basal breast cancers display mRNA up-regulation of BCL-X and MCL1, respectively. Basal cancers possess also more frequently than other sub-sets MCL1 amplifications. Survival outcomes are not significantly different in cancers with higher expression of anti-apoptotic BCL2 mRNAs.
Therapeutic targeting of the apoptotic process in breast cancer sub-types will be improved by a detailed understanding of the core players in the process, including anti-apoptotic BCL2 family proteins. A sub-set of breast cancers harbor amplifications of MCL1 and dysregulations of expression of most family members that could affect the sensitivity to their inhibition by altering the cell’s apoptotic threshold.
Details
- Title: Subtitle
- Breast cancer sub-types display heterogeneity in gene amplification and mRNA expression of the anti-apoptotic members of BCL2 family
- Creators
- Ioannis A. Voutsadakis - Sault Area Hospital
- Resource Type
- Journal article
- Publication Details
- Gene, Vol.857, pp.147179-147179
- DOI
- 10.1016/j.gene.2023.147179
- PMID
- 36627096
- NLM abbreviation
- Gene
- ISSN
- 0378-1119
- eISSN
- 1879-0038
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 03/20/2023
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984806498002771
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