Brk Protects Breast Cancer Cells from Autophagic Cell Death Induced by Loss of Anchorage

• DOI: 10.2353/ajpath.2009.080811
• Publication Date: 2009-08-07T01:55:51Z
• Authors: Amanda J. Harvey; Caroline J. Penni...; Sarah Porter; Rajpal S. Burmi; Dylan R. Edwards; William Court; Suzanne A. Eccles; Mark R. Crompton
• Keywords: Adult; 0301 basic medicine; Cell Survival; 610; Breast Neoplasms; Polymerase Chain Reaction; Gene Expression Regulation, Enzymologic; Pathology and Forensic Medicine; 03 medical and health sciences; Breast cancer; 616; Autophagy; Cell Adhesion; Humans; Cells, Cultured; Aged; Cell Proliferation; Aged, 80 and over; Carcinoma, Ductal, Breast; Middle Aged; Protein-Tyrosine Kinases; Neoplasm Proteins; 3. Good health; Gene Expression Regulation, Neoplastic; Autophagic cell death; Brk; Disease Progression; Female; RNA Interference

Brk, a tyrosine kinase expressed in majority of breast tumors, but not normal mammary tissue, promotes carcinoma cell proliferation. Normal epithelial cells are dependent on cell-cell or cell-matrix interactions for survival and undergo apoptosis after disruption these interactions. Tumor less sensitive to the induction predicted have potential disseminate. We investigated whether Brk has further roles tumor progression by relating its expression grade demonstrating role regulation under non-adherent conditions. was determined reverse transcription PCR RNA extracted from surgical samples human cancers. Breast suspension culture examined when protein levels were suppressed interference. Additionally, effect experimentally overexpressing otherwise Brk-negative assessed. mRNA notably higher 3 as compared with lower grades. In culture, suppression increased rate death, controls, this death program exhibited characteristics autophagy apoptosis. Conversely, experimental whereas kinase-inactive did not. Therefore, enhances suspension, suggesting supporting cancer dissemination.