The role of Rho GTPases in the regulation of the rearrangement of actin cytoskeleton and cell movement

The rearrangement of the actin cytoskeleton has been shown to play a critical role in the development of transformation and malignant phenotype of cancer cells. Rho family GTPases regulate the arrangement of the actin cytoskeleton. By wound-healing assay, we have found that NIH 3T3 fibroblast cells move towards the wound- gaps by extending filopodial and lamellipdial structures at the leading edge of the moving cells. We have inactivated the function of Rho GTPases of v-Ras transformed NIH 3T3 cells by overexpressing Rho GTPase-activating (RhoGAP) domain of RhoGAP of p190. We have observed that inactivation of Rho, Rac and Cdc42 GTPases by overexpressing RHG causes inhibition of: (i) polymerization of actin to form filaments, (ii) formation of lamellipodia, filopodia and stress fibres, (iii) cell motility, (iv) cell spreading and (v) cell-to-cell adhesions. These results further strengthen the current knowledge on the role of Rho, Rac and Cdc42 GTPases in the regulation of the rearrangement of actin cytoskeleton. Our results, for the first time, demonstrate that RhoGAP domain of RhoGAP could be used to study the molecular mechanism of Ras-mediated signalling in growth, differentiation and carcinogenesis.

Factor de crecimiento transformante beta-1: estructura, función y mecanismos de regulación en cáncer / Transforming growth factor beta-1: structure, function and regulation mechanisms in cancer

El factor de crecimiento transformante beta-1 (TGF-b1) es sintetizado por muchas estirpes celulares como linfocitos, macrófagos y células dendríticas, y su expresión regula de manera autócrina o parácrina la diferenciación, proliferación y el estado de activación de éstas y muchas otras células. En general, el TGF-b1 tiene propiedades pleiotrópicas en el contexto de la respuesta inmune durante el desarrollo de infecciones y procesos neoplásicos; sin embargo, los mecanismos de acción y regulación de la expresión de esta citocina aún no se comprenden del todo. En la presente revisión se describen las propiedades biológicas y los procesos moleculares que regulan la expresión del TGF-b1, para entender los efectos de esta citocina durante la proliferación y la diferenciación celular. El conocimiento de los mecanismos moleculares de la regulación del TGF-b1 puede representar una importante estrategia de tratamiento del cáncer. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html

Carcinoma de la vesícula biliar: expresión de productos de los oncogenes C-MYC y RAS-P-21 / Carcinoma of gallblader: expression of products of C-MYC and RAS-P-21 oncogene

The expression of c-myc and p-ras-21 oncogenes was studied using an immunohistochemical method with monoclonal antibodies in 126 samples of gallbladder carcinoma (103 primary tumors and 23 metastatic lesions). Twenty five gallbladder samples without tumor evidence were used as controls. C-myc oncoprotein was positive in one control sample and p-ras-21 oncoprotein was negative in all. Among primary carcinomas c-myc was positive in 9 (9 per cent) and 4 (4 per cent); among metastatic carcinomas c-myc was positive in 6 (26 per cent, p=0.03 vs primary carcinoma) and p-ras-21 in 11 (48 per cent, p <0.001 vs primary carcinoma). There was a non significant association between c-myc and p-ras-21 expression and degree of histological differentiation and levelñ of tumoral infiltration. It is concliuded that c-myc and p-ras-21 oncoprotein expression is observed in less than 10 per cent of primary gallbladder carcinomas and that this expression is significantly higher in metastatic cells

Surface Properties of Cell Membrane in Early Stage of Transformed Cell -I. Early Detection of Transformed Cell by Concanavalin A; II. Properties of Plasma Membrane of Transformed Rat Liver Cell Induced by 3'-Me DAB

The present study was designed in order to investigate the lectin induced cytoagglutination properties of normal and transformed cells and surface alterations in the early stage of the transformed cells by characterizing the structural changes on the hepatoma surface membrane. Rat and rabbit erythrocytes and Sarcoma 180 ascites tumor cells were used for the lectin-induced cytoagglutination. Plotting % agglutination versus concanavalin A(Con A) concentration, sigmoid curves appeared in all cases. alpha-methyl-D-mannopyranoside(alphaMM) inhibited Con A induced cytoagglutination and the degrees of inhibition depended on the cell types and species. When rats were fed a diet containing 0.06% 3'-methyl-4dimethylaminoazobenzene(3'-Me DAB) for 12 weeks, almost all of the rats had solid liver tumors. Polyacrylamide gel electrophoresis of surface membrane proteins of these rat livers and of transplanted tumor cells showed three distinct protein bands, of which two were absent in normal rat livers. The molecular weights of these proteins were 73,000, 66,000, and 57,000 daltons. Antiserum against primary hepatocarcinoma surface proteins precipitated with three membrane proteins obtained from primary hepatocarcinoma cells as well as transplanted hepatocarcinoma cells, suggesting the presence of specific tumor antigens in these cells.