1996 Fiscal Year Final Research Report Summary
Calcitonin receptor polymorphism-function and diseases-
| Project/Area Number |
07807023
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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 | Wakayama Medical College, 2nd Department of Pathology |
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Principal Investigator |
KAKUDO Kennichi Wakayama Medical College, 2nd Department of Pathology, 第2病理学, 教授 (00112037)
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| Project Period (FY) |
1995 – 1996
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| Keywords | calcitonin / calcitonin receptor / gene polymorphism / mammary carcinoma / receptor / race |
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| Research Abstract |
There are three isoforms of calcitonin receptors (CTRs). The first type (type 1) has 465 amino acids in rat and 468 amino acids in porcine. The second type (type 2) has a 39 amino acid insertion in the second extracellular domain. The third type (type 3) has a 16 amino acid insertion in the first intracellular domain. The human CTR which has been isolated from a human ovarian carcinoma cell line belongs to this type 3.
Using RT-PCR with primers whose sequences correspond to the human CTR cDNA,we analyzed the expression of the CTR transcripts in seven human tumor cell lines and surgical specimens. The CTR m-RNA were found in all samples. Transcripts which were 48bp shorter than that of the type 3 were detected, but not transcripts of type 2 and type 3. Since the structure of this CTR is same as that of the type 1, we termed it the human type 1 CTR.PCR studies using human genomic DNA as a template recvealed that the 48bp sequence constitutes an exon. These results indicate that the type 1 and the type 3 human CTRs are generated by alternative splicing and a majority of human CTR transcripts is type 1.
Structural analysis of CTRs from ten cultured human tumor cell lines and 117 human blood samples demonstrated allelic variants at the 1377th nucleotide in the intracellular domain 4, expressing either proline or leucine as the 463th amino acid. It was found that the variant with proline at this site was the more prevalent type of CTR among Japanese population.
The allele frequencies of the calcitonin receptor (CTR) gene were compared between 46 breast cancer patients and 50 controls. The allele frequencies of CTR gene did not differ between them. There was no significant association of CTR allele frequencies histologicaly in invasive breast carcinomas. These results indicate that allelic variants of CTR gene is not significant risk factor to the development of breast carcinoma in Japanese.
Further studies are needed to clear the function of CT or CTR in mammary tissue.
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