2005 Fiscal Year Final Research Report Summary
The role of Stat5 for targeting therapy and chemoprevention in breast cancer
| Project/Area Number |
16591267
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
YAMASHITA Hiroko Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (70332947)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAGUCHI Maho Nagoya City University, Graduate School of Medical Sciences, Research Fellow, 大学院・医学研究科, 臨床研究医 (70381845)
MITA Keiko Nagoya City University, Graduate School of Medical Sciences, Research Fellow, 大学院・医学研究科, 研究員 (70381895)
IWASE Hirotaka Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Professor, 医学薬学研究室, 教授 (40211065)
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| Project Period (FY) |
2004 – 2005
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| Keywords | breast cancer / Stat5 / targeting therapy |
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| Research Abstract |
Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P<0.0001), ER (P=0.02), and progesterone receptor (PR)(P=0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P=0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive had significantly better response to endocrine therapy (P=0.04), and longer survival after relapse (P= 0.0003), that those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.
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