Expression of wild-type p53 stimulates an increase in both Bax and Bcl-xL protein content in HT29 cells.
It has been shown previously that wild-type p53 activity can simultaneously up-regulate Bax, a protein which predisposes cells to programmed cell death (PCD), and down-regulate Bcl-2, a protein which antagonizes PCD. These findings have been interpreted to suggest that correction of the mutant p53 status of some tumor cells may be a means of increasing their sensitivity to chemotherapeutic agents, by increasing their likelihood of undergoing PCD. We show here that when wild-type p53 activity is expressed in HT29 human colon cancer cells by use of a temperature sensitive p53 mutant, Bax levels rise, but so do levels of Bcl-xL protein. These observations indicate that Bcl-2 and Bcl-xL are regulated differently in response to wild-type p53 activity and that, while correction of mutant p53 phenotype may effectively kill cells having Bcl-2 as their major defense against PCD, this is not necessarily the case in cells using Bcl-xL as their primary defense.
Merchant
A K
AK
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0504, USA.
Loney
T L
TL
Maybaum
J
J
D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D019073:HT29 Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D013696:Temperature; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein