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p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells

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Title: p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells
Authors: Dong, Peixin Browse this author
Tada, Mitsuhiro Browse this author
Hamada, Jun-Ichi Browse this author
Nakamura, Akihiro Browse this author
Moriuchi, Tetsuya Browse this author
Sakuragi, Noriaki Browse this author →KAKEN DB
Keywords: Endometrial cancer
p53 Dominant negative mutation
Issue Date: Oct-2007
Publisher: Springer
Journal Title: Clinical & Experimental Metastasis
Volume: 24
Issue: 6
Start Page: 471
End Page: 483
Publisher DOI: 10.1007/s10585-007-9084-8
PMID: 17636407
Abstract: Dominant negative (DN) mutations of tumor suppressor p53 (TP53) are clinically associated with cancer progression and metastasis of endometrial malignancy. To investigate the DN effect on tumor migration and invasion, we generated cells that stably co-expressed wild-type (wt) and R273H DN mutant TP53 (273H cells), and wt and R213Q recessive mutant TP53 (213Q cells), by transfection in endometrial cancer cells HHUA that expressed wt p53. R273H, but not R213Q, repressed wt p53-stimulated transcription of p21, Bax, and MDM2. 273H cells also showed markedly increased in vitro invasion and migration potentials, and displayed reduced Maspin, PAI-1, and KAI1 mRNA expressions as compared with 213Q and wt cells. The induction of wt p53 function by use of Adriamycin resulted in the inhibition of the invasion/migration capacity in association with the up-regulation of p53 target genes to a far greater degree in 213Q and wt cells than in 273H cells. R273H expression in p53-null cancer cell SK-OV-3 and Saos-2 did not significantly affect cell invasion and migration activities. Taken together, these results suggest that transdominance of R273H mutant over wt p53 rather than a gain-of-function promotes tumor metastasis by increasing invasion and migration in HHUA cells.
Rights: The original publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 櫻木 範明

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