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

Dong, Peixin; Tada, Mitsuhiro; Hamada, Jun-Ichi; Nakamura, Akihiro; Moriuchi, Tetsuya; Sakuragi, Noriaki

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

Dong, Peixin; Tada, Mitsuhiro; Hamada, Jun-Ichi et al.

Clinical & Experimental Metastasis, 2007, 24(6), 471-483

Permalink : https://hdl.handle.net/2115/52990

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アクセス権	open access
URI	https://hdl.handle.net/2115/52990
タイトル	p53 dominant-negative mutant R273H promotes invasion and migration of human endometrial cancer HHUA cells
著者	Dong, Peixin ; Tada, Mitsuhiro ; Hamada, Jun-Ichi ; Nakamura, Akihiro ; Moriuchi, Tetsuya ; Sakuragi, Noriaki
著者名 Dong, Peixin
著者名 Tada, Mitsuhiro
著者名 Hamada, Jun-Ichi
著者名 Nakamura, Akihiro
著者名 Moriuchi, Tetsuya
e-Rad_Researcher 70153963 著者名 Sakuragi, Noriaki
言語	英語
キーワード	Endometrial cancer
	p53 Dominant negative mutation
	Gain-of-function
	CP-31398
	migration
	invasion
	adenocarcinoma
発行日	2007-10
出版者	Springer
収録物名	Clinical & Experimental Metastasis
巻(号)	24(6)
ページ	471-483
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	The original publication is available at www.springerlink.com.
PISSN	0262-0898
EISSN	1573-7276
NCID	AA1064065X
関連情報	PMID 17636407
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s10585-007-9084-8