Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells

Abstract

Summary Prostaglandins are synthesized from arachidonic acid by the enzyme cyclo-oxygenase. There are two isoforms of cyclooxygenases: COX-1 (a constitutive form) and COX-2 (an inducible form). COX-2 has recently been categorized as an immediate-early gene and is associated with cellular growth and differentiation. The purpose of this study was to investigate the effects of exogenous dimethylprostaglandin E2 (dmPGE2) on prostate cancer cell growth. Results of these experiments demonstrate that administration of dmPGE2 to growing PC-3 cells significantly increased cellular proliferation (as measured by the cell number), total DNA content and endogenous PGE2 concentration. DmPGE2 also increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. The same results were observed in other human cancer cell types, such as the androgen-dependent LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal carcinoma DiFi cells. In PC-3 cells, the dmPGE2 regulation of the COX-2 mRNA levels was both time dependent, with maximum stimulation seen 2 h after addition, and dose dependent on dmPGE2 concentration, with maximum stimulation seen at 5 [sg ml-'. The non-steroidal anti-inflammatory drug flurbiprofen (5 FM), in the presence of exogenous dmPGE2, inhibited the up-regulation of COX-2 mRNA and PC-3 cell growth. Taken together, these data suggest that PGE2 has a specific role in the maintenance of human cancer cell growth and that the activation of COX-2 expression depends primarily upon newly synthesized PGE2, perhaps resulting from changes in local cellular PGE2 concentrations.

Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-κB activation

“…The speci®c role of CD14 in activation of tumor cells by LPS is under investigation. PGE 2 has been shown to be a growth-promoting factor in certain carcinoma cell lines (Tjandrawinata et al, 1997), and also recently has been shown to inhibit apoptosis in colon carcinoma cells (Sheng et al, 1998). PGE 2 suppresses the immune reaction against tumor cells by modulating production of cytokines such as IL-10 and IL-12 by lymphocytes and macrophages (Kucharzik et al, 1997;Huang et al, 1996Huang et al, , 1998.…”

“…Although COX-2 expression appears to participate in tumor proliferation and progression, few reports have examined modulation of COX-2 expression in carcinoma cells by external factors. Tjandrawinata et al (1997) have shown that exogenous PGE 2 increased COX-2 mRNA expression in human prostatic carcinoma, and Huang et al (1998) have demonstrated COX-2 induction by IL-1b in non-small cell lung cancer cells. LPS has been shown to regulate COX-2 in nonneoplastic cells, such as macrophages (Lee et al, 1992), but our ®nding that LPS can modulate COX-2 expression in a line of carcinoma cells represents a new avenue of investigation.…”

The Cyclooxygenase-2 Inhibitor Celecoxib Induces Apoptosis by Blocking Akt Activation in Human Prostate Cancer Cells Independently of Bcl-2

“…Inhibitor Celecoxib-As evidence indicates that COX-2 is upregulated in many cancer cell lines including prostatic carcinoma (35), we compared the expression of COX-2 in androgenresponsive LNCaP and androgen-nonresponsive PC-3 cell lines vis-à -vis normal human prostate epithelial cells by Western blot analysis. was examined.…”

Glycosylation regulates turnover of cyclooxygenase‐2

“…Although the presence of AA can lead to an increase in COX-2 by indirectly up-regulating its transcription [15,26], the mutant and wild-type COX-2 gene constructs used in this study were under the control of the pcDNA3 plasmid's CMV promoter rather than their native COX-2 promoter. Thus, the increased COX-2 activity in AA-treated cells (shown in Fig.…”