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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/3711

Title: Brk protects breast cancer cells from autophagic cell death induced by loss of anchorage
Authors: Harvey, AJ
Pennington, C
Porter, S
Burmi, RS
Edwards, DE
Eccles, SA
Crompton, MR
Keywords: Breast cancer
Brk
Autophagic cell death
Publication Date: 2009
Publisher: American Society for Investigative Pathology
Citation: Americal Journal of Pathology. 175(3): 1226-1234
Abstract: Brk, a tyrosine kinase expressed in a majority of breast tumors, but not normal mammary tissue, promotes breast carcinoma cell proliferation. Normal epithelial cells are dependent on cell–cell or cell–matrix interactions for survival and undergo apoptosis after disruption of these interactions. Tumor cells are less sensitive to the induction of apoptosis and are predicted to have the potential to disseminate. We investigated whether Brk has further roles in breast tumor progression by relating its expression to tumor grade and demonstrating its role in the regulation of carcinoma cell survival under non-adherent conditions. Brk expression was determined by reverse transcription PCR on RNA extracted from surgical samples of human breast cancers. Breast carcinoma cell survival in suspension culture was examined when Brk protein levels were suppressed by RNA interference. Additionally, the effect of experimentally overexpressing Brk in otherwise Brk-negative breast carcinoma cells was assessed. Brk mRNA expression was notably higher in grade 3 breast tumors, as compared with lower tumor grades. In suspension culture, Brk suppression increased the rate of cell death, as compared with controls, and this cell death program exhibited characteristics of autophagy but not of apoptosis. Conversely, experimental expression of Brk in Brk-negative cells increased cell survival whereas kinase-inactive Brk did not. Therefore, Brk enhances breast carcinoma cell survival in suspension, suggesting a role for Brk in supporting breast cancer cell dissemination.
Description: © 2009 American Society for Investigative Pathology. The full and final published article is available at the link below.
Sponsorship: Brunel Open Access Publishing Fund
URI: http://www.sciencedirect.com/science/article/pii/S0002944010606323
http://bura.brunel.ac.uk/handle/2438/3711
DOI: http://dx.doi.org/10.2353/ajpath.2009.080811
ISSN: 0002-9440
Appears in Collections:School of Health Sciences and Social Care Research Papers
Biological Sciences
Community Health and Public Health
Brunel OA Publishing Fund

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