TPA Induces Transglutaminase C and Inhibits Cell Growth in the Colon Carcinoma Cell Line SW620 (original) (raw)

1997, Biochemical and Biophysical Research Communications

found that the application of TPA markedly inhibited In contrast to most other systems, TPA induced TG C the increase of TG C caused by RA in mouse epidermal activity and protein in SW620 human colon carcinoma cells. Our own results also show that the activation of cells. This induction was accompanied by cell growth PKC inhibits induction of TG C by RA in NIH3T3 cells inhibition and increased apoptosis. The general pro-(manuscript in preparation). However, Keogh et al tein kinase-C inhibitor GF-109203X blocked the inducrecently reported that in a human colon tumor cell line, tion of TG C by TPA, whereas the specific inhibitor of SW620, TPA induced TG C enzyme activity. Induction the PKCa isoform, the indocarbazole Go6976, reduced of transglutaminase C by TPA is quite intriguing since, it by 40%. These PKC inhibitors had similar inhibitory in other cell lines, this agent has been shown to be effects on TPA increased apoptosis and inhibition of inhibitory. According to Birckbichler (14) inhibition of cell growth, suggesting that the observed actions of TG C resulted in an increase of proliferative markers in TPA are mediated by PKC, and a close connection behuman lung cells and our own observations (9) showed tween TG C activity, increased apoptosis and cell that induction of the enzyme paralleled a decrease in growth inhibition. We conclude that TPA may offer cell proliferation. On the basis of these results, it is new approaches in the management of colon cancer reasonable to suggest that induction of TG C is related cell growth. ᭧ 1997 Academic Press to the proliferation status of the cell, namely, transglutaminase C is induced when cell proliferation decreases. In the present study, we wanted to examine Transglutaminases are a family of enzymes that catwhether 1. the induction of TG C by TPA was paralleled alyze the transamidation of glutamine residues of proby a decrease in cell growth; 2. whether induction of teins, resulting in the formation of e-amino(g-glutamyl) the enzyme by TPA and a possible effect on cell growth lysine crosslinks (for review: (1)). Three important involved PKC; and 3. whether the activation of TG C members of this family are plasma transglutaminase was accompanied by increased apoptosis in SW620 or Factor XIII which stabilizes the fibrin clot by crosscells. linking fibrin monomers to fibrin polymers; keratinocyte transglutaminase or TG K which contributes to the formation of the protective cornified envelope of squa-MATERIALS AND METHODS mous epithelia; and tissue transglutaminase or TG C , a ubiquitous cytoplasmic enzyme involved in apoptosis, Cell culture and chemicals. SW620 cells were obtained from the cell adhesion, and nerve regeneration (2-5).