期刊
CANCER RESEARCH
卷 64, 期 19, 页码 6906-6914出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-1767
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资金
- NCI NIH HHS [R01 CA115699, K01 CA87828, R01 CA115699-01A1, R01 CA115699-02, R01 CA115699-03, P30 CA051008, P30 CA51008, K01 CA087828, T32 CA009686, R01 CA115699-04, R01 CA115699-05, R01 CA115699-03S1] Funding Source: Medline
Following DNA damage, human cells arrest primarily in the G(1) and G(2) phases of the cell cycle. Here, we show that after irradiation, human cancer cells with targeted deletion of PTEN or naturally occurring PTEN mutations can exert G(1) and G(2) arrests but are unable to arrest in size. Pharmacological inhibition of phosphoinositol-3-kinase, or mTOR in PTEN-/- cells restored the size arrest, whereas siRNA-mediated depletion of TSC2 in PTEN+/+ cells attenuated the size arrest. Radiation treatment potentiated Akt activation in PTEN-/- but not PTEN+/+ cells. Finally, abrogation of the size arrest via PTEN deletion conferred radiosensitivity both in vitro and in vivo. These results identify a new tumor suppressor gene-regulated, DNA damage-inducible arrest that occurs simultaneously with the G(1) and G(2) arrests but is genetically separable from them. We suggest that aberrant regulation of cell size during cell cycle arrest may be important in human cancer pathogenesis.
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