Human ZNF312b promotes the progression of gastric cancer by transcriptional activation of the K-ras gene

Cited 27 time in scopus
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Title
Human ZNF312b promotes the progression of gastric cancer by transcriptional activation of the K-ras gene
Author(s)
In-Seong Song; Nang Su Oh; H T Kim; Ga-Hee Ha; So-Young Jeong; J M Kim; D I Kim; Hyang Sook Yoo; C H Kim; Nam-Soon Kim
Bibliographic Citation
Cancer Research, vol. 69, no. 7, pp. 3131-3139
Publication Year
2009
Abstract
Gastric cancer ranks second among the most common causes of cancer deaths worldwide. Recent studies reported target molecules that are candidates for new therapeutic interventions; however, their molecular mechanism has not been clearly defined. In this study, we found that ZNF312b plays a role in tumor progression and metastasis in gastric cancer via transcriptional activation of the K-ras oncogene. ZNF312b seems to be specifically overexpressed in gastric cancer tissues and cell lines. The overexpression of ZNF312b induces cancer-like phenotypes, including accelerated proliferation and increased tumor masses in nude mice, which are completely reversed by its knockdown in gastric cancer cell lines, implying direct involvement in gastric tumor progression. From analyses using deletion mutants of ZNF312b and K-ras promoter-driven luciferase reporters, we found that it translocates into the nucleus via the proline-rich domain of its COOH terminus to activate transcription of the K-ras gene, resulting in an enhancement of the extracellular signal-regulated kinase signaling pathway that governs cell proliferation. Taken together, these results suggest that ZNF312b contributes to the promotion of gastric cancer by triggering K-ras oncogene expression. The current study is the first to report that ZNF312b, a novel transcription factor, was associated with tumorigenicity of gastric cancer. This might be a valuable target that could provide new insight into the development of new therapeutic modalities for patients with gastric cancer.
ISSN
0008-5472
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/0008-5472.CAN-08-2240
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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