| Project/Area Number |
09670173
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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 | Tohoku University |
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Principal Investigator |
KIMURA Noriko Tohoku Univ., Sch., Med., Associate Professor, 医学部, 助教授 (80142975)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Breast carcinoma / BRCA1 / chromogranin A / chromogranin B / somatostatin receptor / tumor suppessor gene / immunohistochemistry / in situ hybridization / クロモグラニン / BRCA |
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| Research Abstract |
The familial breast and ovarian tumor suppressor gene BRCA 1 encodes an 1863amino acid protein, The functional domains in the BRCA 1 sequence have perfect granin consensus at BRCA 1 amino acids 1214-1223. BRCA 1 localizes to mamary epthelium and secretary protein. There have been recognized that there are breast carcinomas(ca) with neuroendocrine (NE) differentiation detected by argyrophilic reaction or granin immunostaining. The mechanism of tumor suppression by BRCA 1 is not clarified. The clilnical significance of expression of granins in breast ca. is alsounclear. We immunohistochemically investigated tissue localization of chromogranin A(CgA), chromogranin B (CgB) and BRCA 1 in normal and ca. of the mammary gland to reveal if there is any relationship between expression of BRCA 1 and granins. In the ca. tissues, BRCA I was observed in 100% of noninvasive ductal ca.. and in 88%of invasive ductal ca.. Loss of BRCA 1 immunoreactivity was 12% in the total ca. including I of 11 familial cases. CgA and CgB were not necessarily coexpressed. The cells immunoreactive for CgA were observed in 70% of noninvasive ductal ca. and 23%of invasive ductal ca., and those for CgB were 65% of noninvasive ductal ca. and 39%of invasive ductal ca.. The immunoreactivity of granins was heterogenous and different from that of BRCA 1. With regards to somatostatin receptor type 2A (sstr), we investigated immunohistochemically and also on mRNA using in situ hybridizationmethod. About 60% of breast carcinomas showed sstr immunoreactivity and coexpressed estrogen receptor. Expression of sstr had little correlation to the tumorsize, lymph node metastasis. The possible mechanism of BRCA 1 as a tumor suppressor may relate in part to sstr through granins and some peptides processed from granins.
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