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TCEB3C a putative t...
TCEB3C a putative tumor suppressor gene of small intestine neuroendocrine tumors
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- Edfeldt, Katarina (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery,Uppsala universitet, Endokrinkirurgi
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- Ahmad, Tanveer (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Uppsala universitet, Institutionen för kirurgiska vetenskaper
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- Åkerström, Göran (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery,Uppsala universitet, Endokrinkirurgi
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- Janson, Eva T (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala universitet, Onkologisk endokrinologi
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- Hellman, Per (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery,Uppsala universitet, Endokrinkirurgi
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- Stålberg, Peter (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery,Uppsala universitet, Endokrinkirurgi
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- Björklund, Peyman (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Uppsala universitet, Endokrinkirurgi
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- Westin, Gunnar (författare)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery,Uppsala universitet, Endokrinkirurgi
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(creator_code:org_t)
- 2014
- 2014
- Engelska.
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 21:2, s. 275-284
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Small intestinal neuroendocrine tumors (SI-NETs), formerly midgut carcinoids, are rare and slow-growing neoplasms. Frequent loss of one copy of chromosome 18 in primary tumors and metastases has been observed. The aim of the study was to investigate a possible role of TCEB3C (Elongin A3), currently the only imprinted gene on chromosome 18, as a tumor suppressor gene in SI-NETs, and whether its expression is epigenetically regulated. Primary tumors, metastases, the human SI-NET cell line CNDT2.5, and two other cell lines were included. Immunohistochemistry, gene copy number determination by PCR, colony formation assay, Western blotting, real-time quantitative RT-PCR, RNA interference, and quantitative CpG methylation analysis by pyrosequencing were performed. The large majority of tumors (33/43) showed very low to undetectable Elongin A3 expression and as expected 89% (40/45) displayed one TCEB3C gene copy. The DNA hypomethylating agent 5-aza-2'-deoxycytidine induced TCEB3C expression in CNDT2.5 cells, in primary SI-NET cells prepared directly after surgery, but not in two other cell lines. Also siRNA to DNMT1 and treatment with the general histone methyltransferase inhibitor 3-deazaneplanocin A induced TCEB3C expression in a cell type-specific way. CpG methylation at the TCEB3C promoter was observed in all analyzed tissues and thus not related to expression. Overexpression of TCEB3C resulted in a 50% decrease of clonogenic survival of CNDT2.5 cells, but not of control cells. The results support a putative role of TCEB3C as a tumor suppressor gene in SI-NETs. Epigenetic repression of TCEB3C seems to be tumor cell type-specific and involves both DNA and histone methylation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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