MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells.
The mitogen-activated protein kinase kinase 1/2 (MEK1/2) signalling pathway plays a central role in tumour progression. Small molecules that inhibit MEK1/2 are therefore considered attractive candidates for anti-cancer drugs. However, the exact contributions of MEK1 and MEK2 to the development of pancreatic cancer remain to be established. To differentiate the functions of MEK1 and MEK2 in a cultured pancreatic cancer cell line, we utilised shRNA-mediated knockdown of their two mRNAs individually. We studied the effects of MEK1 and MEK2 knockdown on cell morphology, proliferation, mitotic arrest, and in vitro invasion capability in PC-1.0 cells. The results showed that inhibition of MEK1 expression was an effective and specific approach to inhibit cell proliferation and induce G0/G1 arrest. On the other hand, MEK2 knockdown specially altered cell morphology and inhibited the invasive ability of pancreatic cancer cells. Therefore, MEK1 and MEK2 mediate different biological responses in cultured pancreatic cancer cells. These proteins could become distinct targets for the inhibition of specific cellular functions in the treatment of pancreatic cancer.
Department of Hepato-pancreato-biliary Tumour Surgery, China Medical University Shengjing Hospital, Shenyang, PR China.
Lei
L
Zhou
Xiaodong
X
Tan
Hidenobu
H
Kamohara
Wei
W
Wang
Baosheng
B
Wang
Jingang
J
Liu
Hiroshi
H
Egami
Hideo
H
Baba
Xianwei
X
Dai
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008647:Mesocricetus; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology
D007527:Isoenzymes; D034741:RNA, Small Interfering; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2