CDK4 down-regulation induced by paclitaxel is associated with G1 arrest in gastric cancer cells.
Paclitaxel induces a cell cycle block at G2-M phase by preventing the depolymerization of microtubules and induces p53-independent apoptosis in many cancer cells. We observed that gastric cancer cells treated with paclitaxel have shown a cyclin-dependent kinase (CDK)4 down-regulation. This paclitaxel-induced CDK4 down-regulation resulted in a cell cycle arrest at G1-S phase. To confirm this observation, we prepared stable transfectants that overexpressed CDK4 and analyzed the cell cycle progression. Ectopic expression of CDK4 in SNU cells resulted in a release of paclitaxel-induced G1 arrest. The release of G1 arrest by enforced expression of CDK4 seems to make the cells more sensitive to paclitaxel-induced apoptosis. From this finding, we could then suggest that paclitaxel treatment induces both G1-S and G2-M blocks in the cell cycle progression of gastric cancer cells.
Yoo
Y D
YD
Laboratory of Experimental Therapeutics, Korea Cancer Center Hospital, Seoul.
Park
J K
JK
Choi
J Y
JY
Lee
K H
KH
Kang
Y K
YK
Kim
C S
CS
Shin
S W
SW
Kim
Y H
YH
Kim
J S
JS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins; D016196:S Phase / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D017239:Paclitaxel