Proliferation‐dependent vs. independent programmed cell death of prostatic cancer cells involves distinct gene regulation
- 1 December 1994
- journal article
- research article
- Published by Wiley in The Prostate
- Vol. 25 (6), 301-309
- https://doi.org/10.1002/pros.2990250604
Abstract
Androgen-independent Dunning R-3327 AT-3 rat prostatic cancer cells can be induced to undergo programmed cell death in either a proliferation-dependent or independent manner depending upon the therapeutic agent used. In the present study, 5-fluorodeoxyuridine (5-FrdU) was used to induce proliferation-dependent death of the AT-3 cells via its ability to inhibit thymidylate synthetase. Ionomycin and thapsigargin were used to induce proliferation-independent death of these cells via their ability to sustain an elevation in intracellular free Ca2+. Based upon the temporal sequence of DNA fragmentation, morphologic changes, and loss of cell viability, each of the three test agents, at the doses used, induces the programmed death of AT-3 cells with essentially identical kinetics. Based upon these similarities, comparisons of the pattern of gene expression during the proliferation-dependent (i.e., 5-FrdU-induced) vs. proliferation-independent (i.e., ionomycin and thapsigargin-induced) programmed death of AT-3 cells allow identification of genes whose enhanced expression is involved in the initiation vs. completion of programmed cell death. Based upon this approach, enhanced H-ras and TRPM-2 expression is associated with initiation of proliferation-dependent programmed death of AT-3 cells while enhanced c-myc, calmdulin, and α-prothymosin expression is associated with initiation of proliferation-independent programmed death of these cells. In contrast, enhanced expression of glucose-regulated 78 kilodalton and tissue transglutaminase genes are associated with the completion of programmed cell death, since their expression is enhanced in both proliferation-dependent and independent programmed cell death of AT-3 cells.Keywords
This publication has 31 references indexed in Scilit:
- Differential gene regulation during programmed death (apoptosis) versus proliferation of prostatic glandular cells induced by androgen manipulationEndocrinology, 1993
- Induction of apoptosis in fibroblasts by c-myc proteinCell, 1992
- Role of calcium in the programmed death of rat prostatic glandular cellsThe Prostate, 1990
- “Thymineless” death in androgen-independent prostatic cancer cellsBiochemical and Biophysical Research Communications, 1989
- Acid blobs and negative noodlesNature, 1988
- Activation of a Ca2+−Mg2+‐dependent endonuclease as an early event in castration‐induced prostatic cell deathThe Prostate, 1988
- Induction and activation of tissue transglutaminase during programmed cell deathFEBS Letters, 1987
- Establishment and characterization of seven dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancersThe Prostate, 1986
- Effect of androgen on the transcription of rat prostatic binding protein genesMolecular and Cellular Endocrinology, 1982