期刊
ENDOCRINE-RELATED CANCER
卷 15, 期 3, 页码 817-831出版社
BIOSCIENTIFICA LTD
DOI: 10.1677/ERC-08-0060
关键词
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资金
- NIH [CA75979]
- Doris Factor Molecular Endocrinology Laboratory
- NATIONAL CANCER INSTITUTE [R01CA075979] Funding Source: NIH RePORTER
As human pituitary tumor transforming gene (hPTTG1) is upregulated in endocrine tumors, we studied regulatory mechanisms for hPTTG1 expression. We identified Oct-1-binding motifs in the hPTTG1 promoter region and show Oct-1-specific binding to the hPTTG1 promoter using chromatin immunoprecipitation. We overexpressed Oct-1 and observed similar to 2.5-fold activation of hPTTG1 promoter luciferase constructs (-2642/- 1 and -1717/-1). Transcriptional activation was abrogated by co-transfection of an inactive Oct-1 form lacking the POU domain or by utilizing mutated hPTTG1 promoters or mutants devoid of two Oct-1-binding motifs (-1717/-1mut, -637/-1 or -433/-1). Using biotin-streptavidin pull-down assays, we confirmed Oct-1 binding to the two octamer motifs in the hPTTG1 promoter (-1669/-1631 and -1401/-1361). Endogenous hPTTG1 mRNA and protein increased up to approximately fourfold in Oct-1 transfectants, as measured by real-time PCR and western blot. In contrast, siRNA-mediated suppression of endogenous Oct-1 attenuated both the hPTTG1 mRNA and protein levels. Using confocal immunofluorescence imaging, Oct-1 and hPTTG1 were concordantly upregulated in pituitary (57 and 62%, n=79, P < 0.01) and breast tumor specimens (57 and 42%, n=77, P < 0.05) respectively. The results show that Oct-1 transactivates hPTTG 1, and both proteins are concordantly overexpressed in endocrine tumors, thus offering a mechanism for endocrine tumor hPTTG1 abundance. Endocrine-Related Cancer (2008) 15 817-831
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