Persistent membrane translocation of protein kinase C α during 12-O- tetradecanoylphorbol-13-acetate-induced apoptosis of LNCaP human prostate cancer cells Journal Article
| Authors: | Powell, C. T.; Brittis, N. J.; Stec, D.; Hug, H.; Heston, W. D. W.; Fair, W. R. |
| Article Title: | Persistent membrane translocation of protein kinase C α during 12-O- tetradecanoylphorbol-13-acetate-induced apoptosis of LNCaP human prostate cancer cells |
| Abstract: | Others have reported that the phorbol ester 12-O-tetradecanoylphorbol- 13-acetate (TPA), an activator and down-regulator of most protein kinase C (PKC) isozymes, can induce apoptotic cell death of androgen-sensitive LNCaP but not androgen-insensitive PC-3 or DU 145 human prostate cancer cells. As a first step toward uncovering the mechanism by which TPA induces apoptosis of LNCaP cells, we quantified expression of PKC isozyme mRNAs in unmodified and TPA-resistant LNCaP cells and in naturally TPA-resistant PC-3, PC-3M, and DU 145 cells. All of the cell lines and normal prostate expressed RNAs for PKC α, δ, ε, η, and μ; only DU 145 cells and normal prostate expressed PKC β and Θ RNAs, and none expressed PKC γ. The amount of PKC α RNA and protein was 6- to 38-fold lower, and PKC μ RNA was 4.5- to 16.5-fold higher in unmodified and TPA-resistant LNCaP cells than in the androgen-independent cells. We examined the effects of TPA on PKC α and μ mRNA levels and on membrane translocation of PKC α. Incubation with TPA for 6 h or more induced 95% inhibition of cell growth, a transient 12-fold increase and 5-fold decrease in PKC α and μ mRNA levels, respectively, and prolonged translocation of PKC α to non-nuclear membranes in unmodified LNCaP cells and in TPA-resistant LNCaP cells from which TPA had been removed for 10 days. TPA-resistant LNCaP cells in the continuous presence of TPA, or 24 h after removal of TPA, had down-regulated PKC α and remained resistant to re- addition of TPA. These data demonstrate a strong correlation of the presence and absence of membrane PKC α with apoptosis and resistance to apoptosis, respectively. |
| Keywords: | protein expression; human cell; protein localization; apoptosis; down-regulation; drug resistance, neoplasm; tumor cells, cultured; time factors; prostate cancer; prostatic neoplasms; prostate; immunoblotting; cytoplasm; protein kinase c; rna, neoplasm; enzyme localization; isoenzymes; phorbol 13 acetate 12 myristate; protein kinase c-alpha; tetradecanoylphorbol acetate; rna, antisense; membranes; humans; human; male; priority journal; article |
| Journal Title: | Cell Growth & Differentiation |
| Volume: | 7 |
| Issue: | 4 |
| ISSN: | 1044-9523 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1996-04-01 |
| Start Page: | 419 |
| End Page: | 428 |
| Language: | English |
| PUBMED: | 9052983 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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