2014 Fiscal Year Final Research Report
Hypertension-related, calcium-regulated gene (HCaRG) inhibits ErbB receptor-driven kidney cancer growth
| Project/Area Number |
25830090
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | HCaRG / 腎細胞癌 / 間葉上皮移行 / プログラム細胞死 / ErbB受容体 |
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| Outline of Final Research Achievements |
Hypertension-related, calcium-regulated gene (HCaRG) is mainly expressed in renal proximal tubules and its overexpression in transgenic mice reduces mortality after acute kidney injury. We demonstrate that HCaRG overexpression in mouse RCC cells led to smaller tumor size with less tumor vascularization in a homograft tumor model. Cancer cells overexpressing HCaRG maintain a more differentiated phenotype, thus delaying cell-cycle progression. Additionally, several cells undergo necroptosis with mitotic catastrophe in parallel, occurring independently of apoptosis. Mechanistically, HCaRG promotes de-phosphorylation of HER2/ErbB2, which is mediated by epigenetic gene silencing of EGFR and ErbB3 via promoter methylation. As a result, downstream MAPK and PI3K/AKT/mTOR signaling pathways are inactivated. Taken together, our data suggest a role for HCaRG in the inhibition of tumor progression as a natural inhibitor of the ErbB signals in kidney cancer.
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| Free Research Field |
腎臓病
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