2014 Fiscal Year Final Research Report
The mechanism of ectopic PTH-, but not PTHrP-,production in retroperitoneal tumor
| Project/Area Number |
24591372
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | PTH / 異所性ホルモン産生腫瘍 / 次世代シークエンス法 / マイクロアレイ / CYP24A1 / ATRX |
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| Outline of Final Research Achievements |
We confirmed intratumoral overproduction of PTH, but not PTHrP, in a retroperitoneal malignant fibrous hyperplasia in a patient who showed lethal hypercalcemia by using RT-PCR and immunohistochemical assay. The rearrangements or mutations of the PTH gene were not observed, while several transcriptional factors responsible for PTH gene regulation were markedly affected in their amounts. Our RNA-seq revealed that copy number variation of chromosome 11 where PTH gene resides occurred much more frequently than that in other chromosomes. Further, we found nonsense mutations of ATRX, med1 and USP24 and so on. Lastly, we found that CYP24A1 mRNA was drastically upregulated, suggesting that resultant intratumoral hypovitaminosis D might lead to uncontrollable intratumoral overproduction of PTH protein. Additional oncogenic stimuli such as perturbations of ATRX or med1/USP24 may well resulted in ectopic PTH overproduction.
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| Free Research Field |
内分泌学
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