title: Wild-type p53 is not sufficient for serum starvation-induced apoptosis in cancer cells but accelerates apoptosis in sensitive cells.
abstract: According to the conflicting growth signal model, cells that are driven to proliferate by certain oncogenes undergo apoptosis but not growth arrest upon withdrawal of growth factors. However, we found that the majority of human cancer cell lines continued to proliferate and did not undergo apoptosis following serum withdrawal. As an exeption, wild-type (wt) p53-expressing HCT116 human colon cancer cells underwent apoptosis within 24-36 h of serum deprivation. p53 degradation in human papilloma virus EG-expressing HCT116 cells led to enhanced survival that was not due to growth arrest. These results are consistent with a role for p53 in starvation-induced death in HCT116 cells. However, other cell lines did not undergo apoptosis despite their expression of wt p53. Thus, H460 cells (wt p53) were resistant to starvation-induced death but introduction of the adenovirus EIA oncoprotein induced p53 and also increased sensitivity to serum withdrawal. p53 was not stabilized by E1A and resistance to starvation-induced cell death was observed in E6-expressing H460 cells. These results suggest that although p53 contributes to starvation-induced apoptosis in sensitive (HCT116 and E1A-expressing H460) cancer cell lines, most cancer cells survived despite the presence of wt p53. We conclude that naturally selected human cancer cell lines suppress apoptosis due to conflicting growth signals.
authors.affiliation: UNIV PENN,SCH MED,HOWARD HUGHES MED INST,DEPT MED,LAB MOL ONCOL & CELL CYCLE REGULAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,LAB MOL ONCOL & CELL CYCLE REGULAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,HOWARD HUGHES MED INST,CANC CTR,LAB MOL ONCOL & CELL CYCLE REGULAT,PHILADELPHIA,PA 19104.
authors.forename: M
authors.initials: M
authors.lastname: Blagosklonny
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Somasundaram
authors.forename: W
authors.initials: W
authors.lastname: Eldeiry