Overexpression of the LKB1 gene inhibits lung carcinoma cell proliferation partly through degradation of c-myc protein.
LKB1 encodes a serine/threonine kinase generally inactivated in human lung cancers, which mediates cancer cell proliferation, migration and differentiation, but its biological function has not been completely elucidated. In this study, we demonstrated that LKB1 was associated with a substantial reduction of c-myc expression by using an inducible LKB1 expression system in the LKB1-null lung cell line A549. Nevertheless, the reduction of the c-Myc gene expression was not accompanied by corresponding reduction of mRNAs but protein, which can be abrogated by a proteosome inhibitor (MG132), suggesting that the reduction was associated with their increased degradation rather than transcriptional controls. Our results implied that the expression of c-Myc protein decreased by LKB1 in transfected cells may be a contributory factor in the process of cell proliferation. Overexpression of the LKB1 gene could inhibit the activation of ERK1/2 and STAT3 signaling pathways involved in the cell proliferation. Thus, LKB1-induced functional operation on c-Myc in promoting cell proliferation may occur in a novel mechanism, which may be regulated by ERK1/2 and/or STAT3 signal pathways in human lung carcinoma cells. Furthermore, our results give some insights into the understanding of how LKB1 inactivation contributes to lung carcinogenesis and emphasizes the central role played by LKB1 in lung cancer development.
Liang
Xuan
X
Department of Oncology, First Affiliated Hospital, Xi'an Jiaotong University Medical College, Shaanxi 710061, PR China.
Nan
Ke-Jun
KJ
Li
Zhao-Lun
ZL
Xu
Qing-Zhi
QZ
D000091162:AMP-Activated Protein Kinase Kinases; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control*; D020935:MAP Kinase Signaling System; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000502:physiology*
D016271:Proto-Oncogene Proteins c-myc; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D000091162:AMP-Activated Protein Kinase Kinases