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Type: Journal article
Title: Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans
Author: Bowen, J.
Gibson, R.
Keefe, D.
Cummins, A.
Citation: Pathology, 2005; 37(1):56-62
Publisher: Taylor & Francis
Issue Date: 2005
ISSN: 0031-3025
Statement of
Joanne M. Bowen; Rachel J. Gibson; Dorothy M. Keefe; Adrian G. Cummins
Abstract: Aims: Small intestinal crypt cells rapidly undergo apoptosis in response to cytotoxic drug treatment that results in gastrointestinal toxicity. The Bcl-2 family have been implicated in both positive and negative regulation of intestinal cell apoptosis. The aim of this study was to examine the effect of cytotoxic treatment on Bcl-2 protein expression in patients and rats with tumours. Methods: Four pro- and four anti-apoptotic members of the Bcl-2 family, caspase-3 and p53 were examined in small intestinal crypts before and after treatment in rats and humans. Immunohistochemistry identified changes in protein expression over time, while relative RT-PCR was used to investigate mRNA expression in rat small intestine. Results: Cytotoxic treatment increased p53 and caspase-3 which coincided with elevated levels of apoptosis. Bax and Bak protein and mRNA expression also significantly increased at 6 hours following treatment in rats. Bax and Bak protein increased at day 1 after treatment in humans. Anti-apoptotic Mcl-1 protein decreased within 24 hours. Other Bcl-2 family members showed only modest changes. Conclusion: Increased expression of Bax and Bak but not other Bcl-2 family members is associated with apoptosis in small intestinal crypts and may amplify the sensitivity and susceptibility of crypt cells to chemotherapy-induced enteropathy.
Keywords: Intestinal Mucosa
Intestinal Neoplasms
Membrane Proteins
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Antineoplastic Agents
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Protein p53
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Caspase 3
DOI: 10.1080/00313020400023461
Appears in Collections:Aurora harvest 6
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