PinX1 without the G-patch motif suppresses proliferation, induces senescence, but does not inhibit telomerase activity in colorectal cancer SW480 cells.
Evidence suggests that Pin2/TRF1-interacting protein X1 (PinX1) inhibits telomerase activity in many types of cancer cells. G-patch is a motif in the PinX1 protein; however, the function of G-patch in colorectal cancer cells has not been definitively elucidated. The present study investigated the antitumor activities of different PinX1 fragments in vitro, and explored the molecular mechanisms responsible for these effects. SW480 cells were transfected with pEGFP-A1-PinX1 1-328 (intact) or pEGFP-A1-PinX1 69-328 (truncated). Flow cytometry was used to observe apoptosis and the cell cycle of SW480 cells transfected with intact PinX1 or truncated PinX1. The apoptosis-related proteins, caspase 3, 8 and 9, were detected by western blotting. Our results indicate that both intact and truncated PinX1 induced apoptosis, G1 arrest, and cellular senescence. However, truncated PinX1 showed no effects on telomerase activity. Why PinX1 without G-patch has similar antitumor activities as intact PinX1 remains unclear. The mechanisms of G-patch require elucidation in subsequent studies. Finally, we detected the protein and mRNA levels of PinX1 and caspase 3, 8 and 9 in colorectal cancer specimens and confirmed that levels of PinX1 and caspase 3, 8 and 9 expression were closely linked to the poor prognosis of colorectal cancer.
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Rui
R
Zhang
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Jian
J
Zhao
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Xu
X
Wang
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Li-Li
LL
Wang
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Jian
J
Xu
Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Chun
C
Song
D000328:Adult; D000368:Aged; D017209:Apoptosis; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D018797:Cell Cycle Proteins; C440808:PINX1 protein, human; D025521:Tumor Suppressor Proteins; D019098:Telomerase; D020169:Caspases