| Project/Area Number |
15590317
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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 |
Human pathology
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| Research Institution | Tokai University |
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Principal Investigator |
UMEMURA Shinobu Tokai University, Pathology, Associate Professor, 医学部, 助教授 (20276794)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEKOSHI Susumu Tokai University, Pathology, Associate Professor, 医学部, 助教授 (70216878)
TOKUDA Yutaka Tokai University, Surgery, Professor, 医学部, 教授 (20163975)
OSAMURA Yoshiyuki Tokai University, Pathology, Professor, 医学部, 教授 (10100992)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | breast cancer / ER-negative / HER2-negative / E2F-5 / cell proliferation / Ki-67 / エストロゲンレセプター / human epidermal growth factor receptor |
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| Research Abstract |
Purpose : Our goal was to find genes that are differentially expressed in breast cancers lacking estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) and that might significantly contribute to cell proliferation in these cancers.
Experimental Design : Forty tumor samples consisting of 10 each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancers were analyzed by an oligonucleotide microarray method. Both genes and tumors samples were subjected to hierarchical clustering.
Results : In hierarchical clustering, a gene cluster including CK5/6 corresponded to the tumor cluster containing mostly ER(-)/HER2(-) cancers. ER(-)/HER2(-) cancers displayed 55 overexpressed genes and 102 underexpressed genes. Differentially expressed genes included several cell cycle related genes : overexpression of p16, cdc20, and E2F-5 and underexpression of cyclin D1 and CDK7. Ki-67 gene expression was highest in ER(-)/HER2(-) cancers and correlated with expression of cyclins A, B, and E and cdc20 in individual cancers of all four immunohistochemical groups. Interestingly, expression of the transcriptional factor E2F-5 was correlated with Ki-67 in ER(-)/HER2(-) cancers only. Immunohistochemistry revealed E2F-5 in five of ten ER(-)/HER2(-) cancers, with localization in the cytoplasm but not in the nucleus.
Conclusions : This is the first report demonstrating overexpression in human breast cancer of E2F-5, a transcription factor with roles in terminal differentiation and in p16/ pocket protein-mediated G1 arrest. This result suggests that E2F-5, whether or not it is functioning normally, has a role in IHC-ER(-)/HER2(-) cancers.
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