Evaluation of PKC isoforms expression in thyroid cells lines and effects of a PKC beta II selective inhibitor
Daniela Molè, Mariella Minoia, Federico Tagliati, Maria Chiara Zatelli & Ettore C degli Uberti
Protein kinase C (PKC) is a key enzyme which regulates proliferation, apoptosis and differentiation, representing a pharmacological target for tumor therapy. PKC is a serin/threonin kinase involved in the control of neoplastic transformation, carcinogenesis, neoplastic invasion, chemoresistance. The role of PKC depends on the tissue and on the specific isoform, among the 11 identified so far. In particular, PKC beta II inhibits cell functions, while PKC delta has a protective role. The aim of our study was to verify PKC isoform expression levels in thyroid follicular and parafollicular cell lines, evaluating the effects of a selective PKC beta II inhibitor. We therefore evaluated PKC beta II and PKC delta expression by immunofluorescence in two thyroid follicular cell lines, N-thy-ori (normal follicular cells) and FTC-133 (follicular cancer cells) and in one parafollicular cell line, TT. Both PKC isoforms are expressed in the investigated cell lines with different patterns. In particular, PKC beta II and PKC delta are localized in the cytoplasm in N-thy-ori cells. Treatment with a selective PKC beta II inhibitor in the presence of serum stimulates and in the absence of serum inhibits cell proliferation. In FTC-133 PKC beta II localizes in the cytoplasm and in the nucleus, while PCK delta is exclusively cytoplasmic. Treatment with a selective PKC beta II inhibitor in the presence of serum stimulates and in the absence of serum inhibits cell proliferation. In TT cells, PKC beta II localizes in the nucleus. Treatment with a selective PKC beta II inhibitor in the presence of serum does not influence cell proliferation, while in the absence of serum has an antiproliferative effect. These preliminary data confirm that PKC isoforms are expressed in different cellular compartments depending on the tissue. Moreover, a selective PKC beta II inhibitor has tissue-dependent effects. The stimulatory effect on proliferation in follicular cells in the presence of serum suggests that serum contains growth factors (likely TSH) which profoundly modify the effects of PKC inhibition. Further studies are needed to clarify the role of PKC in thyroid neoplasia.