Restoration of bax in prostate cancer suppresses tumor growth and augments therapeutic cell death induction.
BACKGROUND
Cancer cells are characterized by multiple genetic defects which result in altered rates of cell division, cell death and ability to differentiate. These same molecular alterations may also contribute to therapeutic resistance. We examined the potential contribution of the pro-apoptotic gene, bax, to suppressing the growth of prostate cancer cells.


METHODS
The bax-deficient DU145 prostate cancer cell line was transfected with a hemagluttinin-tagged bax (HA-bax) vector to generate stable expressing bax clones.


RESULTS
Ha-bax clones exhibited a significant reduction in tumor growth compared to vector control and parental cells when xenografted into nude mice. HA-bax clones were significantly more sensitive to cell death induction by cis-diamminedichloroplatinum, etoposide, doxorubicin and gamma-radiation than vector control cells. Sensitivity to paclitaxel remained unaltered in the Ha-bax cells.


CONCLUSIONS
These findings suggest that bax may possess a tumor suppressor function in prostatic glandular epithelial cells and be an important determinant of sensitivity to therapeutic cell death induction.
Honda
T
T
Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Gjertsen
B T
BT
Spurgers
K B
KB
Briones
F
F
Lee
S J
SJ
Hobbs
M L
ML
Meyn
R E
RE
Roth
J A
JA
Logothetis
C
C
McDonnell
T J
TJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects*; D002455:Cell Division / Q000502:physiology; D006388:Hemagglutinins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011836:Radiation Tolerance / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; C494827:Bax protein, mouse; D006388:Hemagglutinins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein