Cyclic AMP Inhibits the Proliferation of Thyroid Carcinoma Cell Lines through Regulation of CDK4 Phosphorylation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Ana Sofia Rocha (Autor) Outra; Sabine Paternot (Autor) Outra; Katia Coulonval (Autor) Outra; Jacques E Dumont (Autor) Outra; Paula Soares (Autor) FMUP; Pierre P Roger (Autor) Outra

Revista

Título: Molecular Biology of the Cell

Vol. 19 Nº 11

Páginas: 4814-4825

ISSN: 1059-1524

Editora: American Society for Cell Biology

Indexação

ISI Web of Knowledge - 41 Citações

Scopus - 43 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

Outras Informações

ID Authenticus: P-003-V9X

DOI: 10.1091/mbc.e08-06-0617

Abstract (EN): How cyclic AMP (cAMP) could positively or negatively regulate G1 phase progression in different cell types or in cancer cells versus normal differentiated counterparts has remained an intriguing question for decades. At variance with the cAMP-dependent mitogenesis of normal thyroid epithelial cells, we show here that cAMP and cAMP-dependent protein kinase activation inhibit S-phase entry in four thyroid carcinoma cell lines that harbor a permanent activation of the Raf/ERK pathway by different oncogenes. Only in Ret/PTC1-positive TPC-1 cells did cAMP markedly inhibit the Raf/ERK cascade, leading to mTOR pathway inhibition, repression of cyclin D1 and p21 and p27 accumulation. p27 knockdown did not prevent the DNA synthesis inhibition. In the other cells, cAMP little affected these signaling cascades and levels of cyclins D or CDK inhibitors. However, cAMP differentially inhibited the pRb-kinase activity and T172-phosphorylation of CDK4 complexed to cyclin D1 or cyclin D3, whereas CDK-activating kinase activity remained unaffected. At variance with current conceptions, our studies in thyroid carcinoma cell lines and previously in normal thyrocytes identify the activating phosphorylation of CDK4 as a common target of opposite cell cycle regulations by cAMP, irrespective of its impact on classical mitogenic signaling cascades and expression of CDK4 regulatory partners.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12