Transforming growth factor-β promotes survival of mammary carcinoma cells through induction of antiapoptotic transcription factor DEC1

被引：90

作者：

Ehata, Shogo

Hanyu, Aki

Hayashi, Makoto

Aburatani, Hiroyuki

Kato, Yukio

Fujime, Makoto

Saitoh, Masao

Miyazawa, Keiji

Imamura, Takeshi

Miyazono, Kohei

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, Tokyo 1130033, Japan

[2] Juntendo Univ, Grad Sch Med, Dept Urol, Tokyo, Japan

[3] Univ Tokyo, Adv Sci & Technol Res Ctr, Genome Sci Div, Tokyo, Japan

[4] Hiroshima Univ, Grad Sch Biomed Sci, Dept Dent & Med Biochem, Hiroshima, Japan

来源：

CANCER RESEARCH | 2007年 / 67卷 / 20期

关键词：

D O I：

10.1158/0008-5472.CAN-07-1522

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Transforming growth factor-beta (TGF-beta) signaling facilitates tumor growth and metastasis in advanced cancer. In the present study, we identified differentially expressed in chondrocytes 1 (DEC1, also known as SHARP2 and Stral3) as a downstream target of TGF-beta signaling, which promotes the survival of breast cancer cells. In the mouse mammary carcinoma cell lines JygMC(A) and 4T1, the TGF-beta type I receptor kinase inhibitors A-44-03 and SB431542 induced apoptosis of cells under serum-free conditions. Oligonucleotide microarray and real-time reverse transcription-PCR analyses revealed that TGF-beta induced DEC1 in these cells, and the increase of DEC1 was suppressed by the TGF-beta type I receptor kinase inhibitors as well as by expression of dominant-negative TGF-beta type II receptor. Overexpression of DEC1 prevented the apoptosis of JygMC(A) cells induced by A-44-03, and knockdown of endogenous DEC1 abrogated TGF-beta-promoted cell survival. Moreover, a dominant-negative mutant of DEC1 prevented lung and liver metastasis of JygMC(A) cells in vivo. Our observations thus provide new insights into the molecular mechanisms governing TGF-beta-mediated cell survival and metastasis of cancer.

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页码：9694 / 9703

页数：10

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