E1A oncogene expression inhibits PTHrP P3 promoter activity and sensitizes human prostate cancer cells to TNF-induced apoptosis.
In the advanced stages of prostate cancer, tumor cells can evolve to become androgen-independent and resistant to injury-induced apoptosis. Tumor cell expression of parathyroid hormone-related protein (PTHrP) may contribute to the apoptosis phenotype. Expression of the adenovirus E1A oncogene repressed PTHrP promoter and mRNA expression in human PC-3 prostate cancer cells and increased the caspase 3 activation and sensitivity of these cells to apoptosis triggered by tumor necrosis factor alpha. These results suggest that strategies aimed at modulating PTHrP expression may increase the efficacy of innate immune effector mechanisms and proapoptotic, therapeutics in prostate cancer.
Asadi
Farrokh K
FK
Department of Biological Sciences, City Colleges of Chicago Harold Washington College, 30 East Lake Street, Chicago, IL 60661, USA. fasadi@ccc.edu
Kukreja
Subhash C
SC
Boyer
Brigitte
B
Valess
Ana-Maria
AM
Cook
James L
JL
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis*; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D017500:Adenovirus E1A Proteins; D044162:Parathyroid Hormone-Related Protein; D014409:Tumor Necrosis Factor-alpha