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Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line

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Title: Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line
Authors: Ochiai, Kazuhiko Browse this author →KAKEN DB
Azakami, Daigo Browse this author
Morimatsu, Masami Browse this author →KAKEN DB
Hirama, Hinako Browse this author
Kawakami, Shota Browse this author
Nakagawa, Takayuki Browse this author →KAKEN DB
Michishita, Masaki Browse this author
Egusa, Ai S. Browse this author
Sasaki, Takanori Browse this author
Watanabe, Masami Browse this author
Omi, Toshinori Browse this author
Keywords: canine
mammary gland tumor
mutation
p53
tetramerization
Issue Date: Jul-2018
Publisher: Spandidos Publications
Journal Title: Oncology reports
Volume: 40
Issue: 1
Start Page: 488
End Page: 494
Publisher DOI: 10.3892/or.2018.6409
PMID: 29750295
Abstract: Mutations in the p53 gene are associated with more than half of all human cancers. These mutations often cause a disruption of the tumor-suppressor function of p53 and induce genomic instabilities. Wild-type p53 requires tetramerization to function as an initiator of cell cycle arrest and apoptosis. Although alterations in p53 tetramerization caused by mutation have been well studied, there are few cell lines containing an endogenous mutation in the tetramerization domain of p53. Here, we report the discovery of a canine mammary gland tumor cell line CTB-m2, which contains the Leu332Gln (L332Q) mutation corresponding to Leu344 in the tetramerization domain of human p53. Although CTB-m2 cells are genetically heterozygous for the Leu332Gln mutation, the mutant mRNA was almost exclusively expressed. CTB-m2 cells showed enhanced cell proliferation compared to wild-type p53-expressing CTB-m cells of the same lineage. A p53 tetramerization reporter assay showed that the ability of the p53 mutant to form tetramers was significantly lower than that of wild-type p53. An immunoblot analysis of cross-linked p53 oligomerized forms demonstrated that the L332Q mutant lacked the ability to form tetramers but retained the ability to form dimers. These data suggest that the p53 mutant cell line CTB-m2 could be a useful tool for analyzing the precise tetramerization mechanisms of p53 and verifying the effects of therapeutic agents against tumors expressing p53 mutants that lack the ability to tetramerize.
Rights: This is self-archiving of the following article: Kazuhiko Ochiai, Daigo Azakami, Masami Morimatsu, Hinako Hirama, Shota Kawakami, Takayuki Nakagawa, Masaki Michishita, Ai S. Egusa, Takanori Sasaki, Masami Watanabe, and Toshinori Omi (2018). Endogenous Leu332Gln mutation in p53 disrupts the tetramerization ability in a canine mammary gland tumor cell line. Oncology reports, 40(1), 488-494.
Type: article
URI: http://hdl.handle.net/2115/72448
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 森松 正美

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