dc.contributor.author	Sandhu, Sumit
dc.contributor.author	Wu, Xiaoli
dc.contributor.author	Nabi, Zinnatun
dc.contributor.author	Rastegar, Mojgan
dc.contributor.author	Kung, Sam
dc.contributor.author	Mai, Sabine
dc.contributor.author	Ding, Hao
dc.date.accessioned	2012-06-01T16:51:59Z
dc.date.available	2012-06-01T16:51:59Z
dc.date.issued	2012-03-27
dc.date.updated	2012-06-01T16:51:59Z
dc.description.abstract	Abstract Background HLTF (Helicase-like Transcription Factor) is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.
dc.description.version	Peer Reviewed
dc.identifier.citation	Molecular Cancer. 2012 Mar 27;11(1):18
dc.identifier.doi	http://dx.doi.org/10.1186/1476-4598-11-18
dc.identifier.uri	http://hdl.handle.net/1993/7249
dc.language.rfc3066	en
dc.rights	open access	en_US
dc.rights.holder	Sumit Sandhu et al.; licensee BioMed Central Ltd.
dc.title	Loss of HLTF function promotes intestinal carcinogenesis
dc.type	Journal Article

Loss of HLTF function promotes intestinal carcinogenesis

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