Concomitant activation of the JAK/STAT3 and ERK1/2 signaling is involved in leptin-mediated proliferation of renal cell carcinoma Caki-2 cells.
Obesity is considered one of the risk factors for many cancers. Serum leptin levels are often elevated in obese people. Leptin has been reported to act as a mitogenic agent and promote renal cancer cell proliferation, whereas the detailed mechanisms still remain to be elucidated. The purpose of this study is to investigate the proliferation and mobility effects in leptin-treated Caki-2 renal cell carcinoma and analyze the alterations of leptin-inducible STAT3 pathways and mitogenic signaling ERK pathways. Our results indicate the constitutive expression of leptin receptor could not be upregulated upon the stimulation of leptin in Caki-2 cells. Leptin increases the proliferation and mobility capabilities of Caki-2 cells via upregulating the expression of both phosphor-ERK and phosphor-STAT3 and these two pathways could be partially abolished by inhibition of the activation of JAK-STAT3 and completely abrogated by inhibition of ERK1/2 pathways. Our results also suggest that mitogenic actions of leptin are not the consequence of altered its receptor expression; whereas the cellular proliferation appears to be working through the cross-talking of JAK-STAT3 and ERK1/2 pathways in renal cell carcinoma caki-2 cells.
Li
Lei
L
Institute of Urology, The 1st Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Gao
Ye
Y
Zhang
Lin-Lin
LL
He
Da-lin
DL
D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D009765:Obesity / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D020738:Leptin; D050796:STAT3 Transcription Factor; D053613:Janus Kinase 1; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases