Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells

被引：31

作者：

Ikeda, Osamu ^{[1
]}

Mizushima, Akihiro ^{[1
]}

Sekine, Yuichi ^{[1
]}

Yamamoto, Chikako ^{[1
]}

Muromoto, Ryuta ^{[1
]}

Nanbo, Asuka ^{[1
]}

Oritani, Kenji ^{[2
]}

Yoshimura, Akihiko ^{[3
]}

Matsuda, Tadashi ^{[1
]}

机构：

[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Sapporo, Hokkaido, Japan

[2] Osaka Univ, Dept Hematol & Oncol, Grad Sch Med, Osaka, Japan

[3] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo, Japan

来源：

CANCER SCIENCE | 2011年 / 102卷 / 04期

关键词：

TRANSDUCING ADAPTER PROTEIN-2; NONRECEPTOR TYROSINE KINASE; GROWTH; CARCINOMA; SUBSTRATE; ADHESION; CLONING;

D O I：

10.1111/j.1349-7006.2010.01842.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Signal-transducing adaptor protein (STAP)-2 is a recently identified adaptor protein that contains Pleckstrin homology and Src homology 2-like domains, and is also known to be a substrate of breast tumor kinase (Brk). In a previous study, we found that STAP-2 upregulated Brk-mediated activation of signal transducer and activator of transcription (STAT) 3 in breast cancer cells. Here, we examined the involvement of STAP-2 in Brk-mediated STAT5 activation in breast cancer cells. Ectopic expression of STAP-2 induced Brk-mediated transcriptional activity of STAT5. Furthermore, STAP-2-knockdown in T47D breast cancer cells induced a marked decrease in proliferation that was as strong as that after Brk- or STAT5b-knockdown. Regarding the mechanism, the Pleckstrin homology domain of STAP-2 is likely to participate in the process by which Brk phosphorylates and activates STAT5. Taken together, our findings provide insights toward the development of novel therapeutic strategies as well as novel prognostic values in breast carcinomas. (Cancer Sci 2011; 102: 756-761)

引用

页码：756 / 761

页数：6

共 26 条

[1] Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients [J].

Aubele, M. ;

Walch, A. K. ;

Ludyga, N. ;

Braselmann, H. ;

Atkinson, M. J. ;

Luber, B. ;

Auer, G. ;

Tapio, S. ;

Cooke, T. ;

Bartlett, J. M. S. .

BRITISH JOURNAL OF CANCER, 2008, 99 (07) :1089-1095

[2] BRK tyrosine kinase expression in a high proportion of human breast carcinomas [J].

Barker, KT ;

Jackson, LE ;

Crompton, MR .

ONCOGENE, 1997, 15 (07) :799-805

[3] STATs in oncogenesis [J].

Bowman, T ;

Garcia, R ;

Turkson, J ;

Jove, R .

ONCOGENE, 2000, 19 (21) :2474-2488

[4] Signal transducers and activators of transcription as regulators of growth, apoptosis and breast development [J].

Bromberg, J .

BREAST CANCER RESEARCH, 2000, 2 (02) :86-90

[5] Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA binding ability [J].

Derry, JJ ;

Richard, S ;

Carvajal, HV ;

Ye, X ;

Vasioukhin, V ;

Cochrane, AW ;

Chen, TP ;

Tyner, AL .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (16) :6114-6126

[6] Stat5a and Stat5b: fraternal twins of signal transduction and transcriptional activation [J].

Grimley, PM ;

Dong, F ;

Rui, H .

CYTOKINE & GROWTH FACTOR REVIEWS, 1999, 10 (02) :131-157

[7] Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation [J].

Harvey, AJ ;

Crompton, MR .

ONCOGENE, 2003, 22 (32) :5006-5010

[8] Developing a Mammary Gland is a Stat Affair [J].

Hennighausen, Lothar ;

Robinson, Gertraud W. ;

Wagner, Kay-Uwe ;

Liu, Xiuwen .

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 1997, 2 (04) :365-372

[9] STAP-2 negatively regulates both canonical and noncanonical NF-κB activation induced by Epstein-Barr virus-derived latent membrane protein 1 [J].

Ikeda, Osamu ;

Sekine, Yuichi ;

Yasui, Teruhito ;

Oritani, Kenji ;

Sugiyma, Kenji ;

Muromoto, Ryuta ;

Ohbayashi, Norihiko ;

Yoshimura, Akihiko ;

Matsuda, Tadashi .

MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (16) :5027-5042

[10] Interactions of STAP-2 with Brk and STAT3 Participate in Cell Growth of Human Breast Cancer Cells [J].

Ikeda, Osamu ;

Sekine, Yuichi ;

Mizushima, Akihiro ;

Nakasuji, Misa ;

Miyasaka, Yuto ;

Yamamoto, Chikako ;

Muromoto, Ryuta ;

Nanbo, Asuka ;

Oritani, Kenji ;

Yoshimura, Akihiko ;

Matsuda, Tadashi .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (49) :38093-38103

← 1 2 3 →