Regulation of bombesin-stimulated cyclooxygenase-2 expression in prostate cancer cells.
Bottom Line: Although BBS stimulates nuclear factor-kappaB (NF-κB) in PC-3, NF-κB does not regulate GRPR-mediated COX-2 expression.The p38MAPK pathway increases BBS-stimulated COX-2 expression by slowing the degradation of COX-2 mRNA.Expression of recombinant GRPR in the androgen-sensitive cell line LNCaP is sufficient to confer BBS-stimulated COX-2 expression via the p38MAPK and PI3K/Akt pathways.
Affiliation: Department of Surgery, Univ. of Texas Medical Branch, 301 Univ. Blvd., Galveston, TX 77555, USA.Show MeSH
Related in: MedlinePlus
Mentions: The cellular levels of COX-2 mRNA can be regulated both by enhanced gene transcription and inhibition of message degradation [31,32]. To determine whether BBS treatment enhanced COX-2 gene transcription, PC-3 cells were first transiently transfected with a transcription reporter construct consisting of 1.4 kb of the human COX-2 promoter coupled to a luciferase gene and then stimulated with BBS over a time course. BBS induced a time-dependent increase (1.4- to 2.3-fold) in COX-2 promoter activity when compared to vehicle-treated control cell cultures (Figure 4A). To determine whether the p38MAPK or PI3K/Akt pathways were involved in BBS-stimulated COX-2 transcription, cells were pretreated with SB203580 (10 μM) or LY294002 (25 μM) for 30 min followed by a 6-h treatment with BBS (10 nM). Compared to BBS treatment alone, LY294002 inhibited approximately 50% of the increase in BBS-stimulated luciferase activity (Figure 4B). In contrast, SB203580 had no effect on BBS-stimulated COX-2 promoter activity (Figure 4B), suggesting that the PI3K/Akt pathway, not the p38MAPK pathway, is involved in BBS-induced COX-2 gene transcription in PC-3 cells.
Affiliation: Department of Surgery, Univ. of Texas Medical Branch, 301 Univ. Blvd., Galveston, TX 77555, USA.