Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

BAG-1 is up-regulated in colorectal tumour progression and promotes colorectal tumour cell survival through increased NF-kappaB activity.

Clemo NK, Collard TJ, Southern SL, Edwards KD, Moorghen M, Packham G, Hague A, Paraskeva C, Williams AC

Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.

Although expression of the anti-apoptotic protein Bcl-2-associated athanogene-1 (BAG-1) has been reported as up-regulated in a number of malignancies, we show for the first time that BAG-1 is over-expressed in medium/large-sized colorectal adenomas and carcinomas compared with normal epithelium. To investigate whether expression of BAG-1 is important for colorectal tumour cell survival, microarray analysis was carried out on the HCT116 colorectal carcinoma cell line following transfection with BAG-1 small interfering RNA (siRNA). Analysis identified altered expression of a subset of potential nuclear factor-kappaB (NF-kappaB)-regulated genes. Furthermore, knock down of BAG-1 was shown to inhibit NF-kappaB transcriptional activity. Inhibition of NF-kappaB activity using BAG-1 siRNA or the NF-kappaB inhibitor BAY-117082 suppressed HCT116 cell yield and induced apoptosis; combined treatment had no additive effect, suggesting that the decrease in cell yield associated with knock down of BAG-1 expression is mediated via inhibition of NF-kappaB. Of clinical relevance, BAG-1 siRNA sensitized colorectal carcinoma cells to apoptosis induced by potential therapeutic agent TRAIL as well as tumour necrosis factor-alpha, both inducers of NF-kappaB activity. In summary, knock down of BAG-1 leads to inhibition of NF-kappaB, identifying BAG-1 as a novel regulator of NF-kappaB. It is proposed that, by inhibiting NF-kappaB, suppression of BAG-1 could represent a novel strategy to impede colorectal cancer cell survival and as an adjuvant increase sensitivity to current therapeutic regimes.

Published 2 April 2008 in Carcinogenesis, 29(4): 849-57.
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