ABSTRACT
A linhagem tumoral Y1, originada de adrenocórtex decamundongo responde a FGF2 (Fator de Crescimento de Fibroblasto), possui o proto-oncogene c-ki-ras amplificado e a proteína c-Ki-Ras super-expressa e ativa (c-Ki-Ras-GTP). Em trabalhos anteriores mostramos que esta lesão genética causa ativação constitutiva da via de sinalização: c-Ki-Ras-GTP®PI3K®Akt (Forti et al. 2002). Por outro lado, a ativação da via de Raf® MEK®ERK, permanece estritamente dependente de estímulos de FGF2 (Rocha et al. 2003). Neste trabalho mostramos, primeiro, que estímulos de FGF2 ativam transientemente a via c-Ki-Ras-GTP®PI3K®Akt para níveis superiores aos expressos constitutivamente. Segundo, a ativação transiente de c-Ki-Ras-GTP por FGF2 permite a ativação da via de ERK1/2. Terceiro, os níveis basais elevados de c-Ki-Ras-GTP inibem a ativação da proteína c-H-Ras, pois células Y1 expressando o mutante negativo RasN17 apresentam uma rápida e transiente ativação de c-H-Ras-GTP após tratamentos de FGF2. Estes estudos das vias de sinalização acionadas por FGF2 em células adrenais tumorais Y1 podem fornecer novos alvos para o desenvolvimento de drogas de interesse para terapia oncogênica.
Subject(s)
Animals , Mice , Adrenal Cortex Neoplasms/genetics , /genetics , Genes, ras/genetics , Signal Transduction/genetics , Adrenal Cortex Neoplasms/pathology , Cell Line, Tumor , Cell Transformation, Neoplastic , Gene Amplification , Gene Expression Regulation, NeoplasticABSTRACT
A large number of DNA sequencing projects all over the world have yielded a fantastic amount of data, whose analysis is, currently, a big challenge for computational biology. The limiting step in this task in the integration of large volumes of data stored in highly heterogeneous repositories of genomic and cDNA sequences, as well as gene expression results. Solving this problem requires automated analytical tools to optimize operations and efficiently generate knowledge. This paper presents an generic flow model, called GenFlow, that can tackle this analytical task.
Subject(s)
Humans , Base Sequence , Computational Biology , Molecular Biology , Computer Simulation , Models, Biological , Molecular Sequence DataABSTRACT
ACTH induces the expression of fos and jun proto-oncogene family members in the mouse Y-1 adrenocortical cell fine. PMA (phorbol-12-myristate-l3-acetate) closely mimics these inductive effects of ACTH. On the other hand, cAMP derivatives are not effective in inducing the fos and jun genes. These results suggest that ACTH receptors are likely to activate signaling routes other than the classical cAMP/protein kinase A in order to induce FOS and JUN proteins. We hypothesize that induction of FOS and JUN proteins is likely to be important in the trophic response of adrenocortical cells to ACTH.
Subject(s)
Animals , Mice , Adrenocorticotropic Hormone/pharmacology , Proto-Oncogene Proteins c-fos , Proto-Oncogene Proteins c-jun , Cyclic AMP , Protein Kinases , Receptors, Corticotropin/metabolism , Tetradecanoylphorbol AcetateABSTRACT
Introduz alguns dados biográficos sobre o professor José Moura Gonçalves e transcreve a entrevista por ele concedida a Erney P. Camargo, Hugo Armelin e Vera Rita da Costa, apresentando sua trajetória como pesquisador num dos grupos pioneiros da bioquímica brasileira, o do professor Baeta Vianna.(MAM)
Subject(s)
Biochemistry , Research Personnel , Science/history , Brazil , History of MedicineABSTRACT
A genetic approach was adopted to analyze the cell cycle G(O)(G (1) (S transition in mouse Balb/ 3T3 fibroblasts (clone A3l). We designed selection procedures to isolate revertant from the EJ-ras transformed Balb/3T3 ribroblasts that had recovered strict -control of the G(O) ( G(1), transition by serum growth factors. The aim was to uncover phenotypic traits associated with malignancy (high growth rate G(1) phase shortening and high tumorigenicity) that segregate independently.