Regulation of actin organisation by TGF-beta in H-ras-transformed fibroblasts

The actin cytoskeleton undergoes architectural changes during the processes of cell transformation and tumourigenesis, Transforming growth factors bet a arrest cell cycle progression, regulate differentiation and modulate the onset of oncogenesis and tumourigenesis. Here, we investigated the direct r ole of transforming growth factor beta-1 in altering the transformed phenot ype and regulating the actin organisation of oncogenic fibroblasts that con stitutively or inducibly express the H-ras oncogene, Following transforming growth factor P-l treatment, these transformed fibroblasts undergo a drama tic morphological alteration that includes a discrete reorganisation of the ir actin cytoskeleton and focal adhesions, Quantitative biochemical analysi s demonstrated that transforming growth factor P-l potently induced polymer isation of globular to filamentous:actin, thus corroborating the morphologi cal analysis, The effect of transforming growth factor beta-1 on the cytosk eleton correlates with the ability of this cytokine to suppress anchorage-i ndependent growth of the transformed fibroblasts, Furthermore, transforming growth factor P-l upregulates considerably the levels of the RhoB small GT Pase and less the RhoA levels, Finally, The Rho GTPase inhibitor, C3 exotra nsferase, blocks the ability of TGF-beta 1 to induce cytoskeletal reorganis ation, These findings indicate that transforming growth factor beta can reg ulate cell morphology and growth in a concerted manner possibly via mechani sms that control the actin cytoskeleton.