Angiotensin II does not stimulate proliferation of rat thyroid PC Cl3 cell line

Abstract

In PC Cl3 cells, a rat thyroid cell line, angiotensin (Ang II) activates the atypical protein kinase C-z (PKC-z) and the extracellular signal-regulated kinase (ERK) pathways. We here studied the Ang II effects on PC Cl3 cell proliferation. It was found that Ang II: (1) induced the phosphorylation of protein kinase B (PKB), (2) induced the growth-related early gene c-fos expression, (3) enhanced the cyclin E and p27 kip expression, (4) had no effects on Cdk2, and (5) did not affect the transition from G0/G1 to S phase. Inhibition of phosphoinositide-3kinase by LY294002 further increased the effect of Ang II on p27 kip induction, whilst PKCs inhibition by GF109203X decreased such effect. The role of PKC-z was recognized by the use of a synthetic myristoylated peptide with sequences based on the endogenous PKC-z pseudosubstrate and by PKC-z downregulation using the small interfering RNA (siRNA). Insulin had a replicating effect on PC Cl3 cells, induced the phosphorylation of PKB, decreased p27 kip expression and had no effect on the PKC-z cytosol-to-membrane translocation. PC Cl3 cell proliferation was induced more potently by simultaneous stimulation with insulin and Ang II than by stimulation with insulin alone, and the effect on p27 kip expression was similar to that obtained with insulin only. These observations demonstrate that in PC Cl3 cells Ang II causes a block in G1 phase, although both ERK and PKB pathways are activated, and this effect may be due to the upregulation of p27 kip and PKC-z operativity.

PKC‐ε‐dependent cytosol‐to‐membrane translocation of pendrin in rat thyroid PC Cl3 cells

“…Insulin (1 µg/ml for 5–80 min) was able only to cause the translocation of novel PKC‐δ and ‐ε (Fig. 7B); as previously shown (Romano et al, 2006) insulin did not affected the translocation of atypical PKC‐ζ, which was used as an internal control to confirm equal protein loading in Western blots showing protein translocations (Fig. 7B).…”

Local thyroid renin–angiotensin system in experimental breast cancer

“…However, recent studies showed that AngII activated ERK signal transduction pathway and induced c-fos expression without acting as a mitogen in PC Cl3 cells. Thus, although both ERK and PI3K/Akt pathways are activated, the effects AngII in PC Cl3 proliferation are not evident (Romano et al, 2006). Therefore, this could be a point of connection between the TSHR and AT1 receptor, although to our view, there remains a deep Table 1 Circulating levels of TSH and fT 4 in control rats, rats treated with NMU that did not develop mammary tumors (NMU non-BC) and rats treated with NMU that developed mammary tumors (NMU BC).…”