期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 177, 期 3, 页码 1503-1513出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090651
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- American Lung Association [HL090156, HL079574-06S1, CA112405, CA105152]
- Barrett Cancer Center Plot
K-RAS mutations are found in approximately 30% of lung cancers. The transcription factor Kruppel-like Factor 5 (KLF5) has been shown to mediate cellular transformation signaling events downstream of oncogenic RAS in other cancers, but a role for KLF5 in lung tumorigenesis has not been defined. We show here that knockdown of KLF5 expression significantly decreased anchorage-independent growth, but did not affect proliferation of human lung adenocarcinoma cells. Moreover, K1f5 is not required for lung tumor formation in an inducible oncogenic K-Ras(G12D) mouse model of lung tumorigenesis, and non-small cell lung cancer patients expressing high levels of KLF5 (21/258) have a significantly better disease-specific survival than those with intermediate to no KLF5 expression. Further, KLF5 knockdown in K-RAS-mutant human lung cancer cells resulted in a fivefold increase in ATP-binding cassette, subfamily G (WHITE), member 2 (ABCG2), an anthracycline drug transporter, which lead to significantly increased resistance to doxorubicin treatment, a chemotherapeutic agent clinically used to treat lung cancer. In summary, while KLF5 is not required for oncogenic mutant K-Ras-induced lung tumorigenesis, KLF5 regulation of ABCG2 expression may be important for chemotherapeutic resistance and patient survival. (Am J Pathol 2010. 177:1503-1513; DOI: 10.2353/ajpath.2010.000651)
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