Differential effects of protein kinase C agonists on prostaglandin production and growth in human breast cancer cells

  title={Differential effects of protein kinase C agonists on prostaglandin production and growth in human breast cancer cells},
  author={A. J. Boorne and N. Donnelly and M. Schrey},
  journal={Breast Cancer Research and Treatment},
A regulatory role for protein kinase C (PKC) and eicosanoids has been implicated in the control of breast cancer cell growth and function. Here we report on the effects of the two PKC agonists 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and bryostatin 1 on arachidonic acid metabolism, prostaglandin E2 (PGE2) production, and growth in MDA MB 231 human breast cancer cells. TPA caused a dose-dependent increase in PGE2 production which was maximal at 100 nM and which was blocked in the presence of… Expand
Comparison of stearidonic acid and alpha-linolenic acid on PGE2 production and COX-2 protein levels in MDA-MB-231 breast cancer cell cultures.
Although PGE2 production in MDA-MB-231 breast cancer cells was not significantly different between the SDA and LNA treatments, SDA was more effective than LNA in converting into LC n-3 PUFAs and in reducing COX-2 protein and mRNA levels. Expand
Bryostatin has proved to be a very potent antitumor-promoting agent, and a very promising anticancer drug, and it has provided curative levels of activity against a variety of murine experimental cancer systems. Expand


Regulation of arachidonic acid metabolism, aromatase activity and growth in human breast cancer cells by interleukin‐1β and phorbol ester: Dissociation of a mediatory role for prostaglandin E2 in the autocrine control of cell function
The cyclooxygenase pathway does not play a mediatory role during the inhibition of cell growth and the induction of aromatase activity by IL‐1β and TPA, and the cytokine greatly potentiated PGE2 production in the presence of TPA. Expand
Evidence for a role for protein kinase C in the modulation of bombesin-activated cellular signalling in human breast cancer cells
Data support an inhibitory role for PKC in the regulation of phosphoinositide hydrolysis and [Ca2+]i in breast cancer cells and provide a potential mechanism for feedback regulation of this signalling pathway in these cells. Expand
Prostaglandin E2 production and metabolism in human breast cancer cells and breast fibroblasts. Regulation by inflammatory mediators.
Breast fibroblasts, particularly under the influence of inflammatory mediators, provide a potentially rich source for PGE2 production in breast tumours, whereas significant contributions from the epithelial tumour component may be restricted to cancer cells exhibiting an invasive phenotype. Expand
Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines.
The effects of the protein kinase C (PKC) activators, phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of humanExpand
Phorbol ester and bryostatin effects on growth and the expression of oestrogen responsive and TGF-beta 1 genes in breast tumour cells.
The inhibitory effects of TPA on the growth stimulation of MCF-7 cells by oestradiol was not due to a general inhibition of the expression of oestrogen responsive genes and the effect of bryostatin, added simultaneously or after TPA, was partially reversed, suggesting brystatin does not simply mimic TPA in this system. Expand
Stimulation of arachidonic acid release and prostaglandin synthesis by bryostatin 1.
It is found that bryostatin 1 could inhibit the effect of TPA both in stimulation of arachidonic acid release and in the induction of prostaglandin H synthase. Expand
Bryostatin 1, an activator of protein kinase C, mimics as well as inhibits biological effects of the phorbol ester TPA in vivo and in vitro.
It is suggested that bryostatin 1 might inhibit a specific 'Ca2+-component' of TPA action, which is needed for the conversion step (first stage of promotion) of multistage carcinogenesis. Expand
The role of protein kinase C isoenzymes in the growth inhibition caused by bryostatin 1 in human A549 lung and MCF‐7 breast carcinoma cells
The results suggest that the susceptibility of adenocarcinpma cells towards bryostatin‐induced growth delay are determined by cellular levels of PKCs‐α and/or −ζ and not intrinsically related to differences in redistribution or down‐regulation of specific PKC isoenzymes. Expand
Protein kinase C modulates the amounts of IL-1 receptor mRNA in human lung fibroblasts.
It is suggested that PKC activity plays an important role in the modulation of IL-1R expression by showing that changes in the numbers ofIL-1 binding sites on human lung fibroblasts are paralleled by changes in IL- 1R mRNA. Expand
Differential effects of bryostatins and phorbol esters on arachidonic acid metabolite release and epidermal growth factor binding in C3H 10T1/2 cells.
The findings on arachidonic acid metabolite release argue against transient activation of the protein kinase C pathway as the sole explanation of bryostatin 1 action and indicate differences in the structure-activity relations of the brystatins for the phorbol ester-mimetic and phorbl ester -inhibitory actions. Expand