RESUMO
The estrogen receptors (ERs) are ligand-inducible transcription factors that play key roles in the control of growth and differentiation in reproductive tissues. We showed that the novel Dbl family proto-oncoprotein Brx enhances ligand-dependent activity of ERalpha via a Cdc42-dependent pathway. Brx also significantly enhances ligand-dependent activity of ERbeta. This enhancement is not affected by inhibition of p44/42 mitogen-activated protein kinase (MAPK) activation by PD98059. However, addition of the p38 MAPK inhibitor SB202190 abrogates the enhancement of ERbeta activity by Brx, showing that p38 MAPK activity is required for the enhancement of ERbeta function by Brx. In COS-7 cells, transfection of Brx leads to activation of endogenous p38 MAPK activity. Co-expression of the beta2 isoform of human p38 MAPK and a constitutively active form of the p38 MAPK kinase MKK6 (MKK6-EE) synergistically augments ligand-dependent activity of ERbeta. Our findings suggest that p38 MAPKs may be important regulators of ERbeta activity.
Assuntos
Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas , Receptores de Estrogênio/metabolismo , Proteínas de Ancoragem à Quinase A , Proteínas Adaptadoras de Transdução de Sinal , Animais , Western Blotting , Células COS , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Inibidores Enzimáticos/farmacologia , Receptor beta de Estrogênio , Flavonoides/farmacologia , Genes Reporter , Humanos , Imidazóis/farmacologia , Immunoblotting , Ligantes , MAP Quinase Quinase 6 , Sistema de Sinalização das MAP Quinases , Antígenos de Histocompatibilidade Menor , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Fosforilação , Plasmídeos/metabolismo , Ligação Proteica , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Distribuição Tecidual , Ativação Transcricional , Transfecção , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
OBJECTIVE: We previously identified a protein, Brx, that interacted with estrogen receptor alpha. Sequence analysis determined that Brx is a novel member of the Dbl family of oncoproteins involved in signaling pathways that regulate cell growth. Because the Brx protein was found to be highly expressed in hormoneresponsive breast epithelium, the objective of this study was to determine whether Brx was expressed in both normal and neoplastic ovarian tissues. STUDY DESIGN: A polyclonal antiserum directed against the Brx protein was used to perform immunolocalization on sections from 5 normal ovaries and 20 ovarian neoplasms. Chromosomal localization of the brx gene was accomplished by means of fluorescence in situ hybridization. Northern and Western blot analyses were performed on extracts prepared from human ovaries. RESULTS: Brx protein was localized to the cytoplasm of granulosa cells from mature graafian follicles, the corpus luteum, and islands of hilar cells in normal ovaries. In tumors with low malignant potential and ovarian carcinomas the neoplastic epithelium stained strongly for Brx protein. Northern and Western blot analyses, respectively, confirmed expression of Brx messenger ribonucleic acid and protein in normal ovary. Finally, the brx gene was localized to 15q25. CONCLUSION: The proto-oncogene brx is expressed in specific normal human ovarian tissues and is also present in ovarian epithelial neoplasms.
Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Oncogênicas/genética , Neoplasias Ovarianas/genética , Ovário/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas de Ancoragem à Quinase A , Proteínas Adaptadoras de Transdução de Sinal , Northern Blotting , Western Blotting , Carcinoma/imunologia , Carcinoma/patologia , Cromossomos Humanos Par 15 , Epitélio/imunologia , Epitélio/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígenos de Histocompatibilidade Menor , Proteínas Oncogênicas/biossíntese , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Ovário/imunologia , Ovário/patologia , Proto-Oncogene MasRESUMO
A patient with pharyngitis progressive to Toxic Shock-Like Syndrome presented to the emergency department with a chief complaint of lower extremity paralysis. This paraplegia was completely reversed with the administration of intravenous glucose. Hypoglycemia-induced paraplegia has not previously been reported in the medical literature, and this report emphasizes the importance of considering low-blood glucose as a potential etiology for patients who present with these neurological symptoms.
