Rho GTPases are over-expressed in human tumors

Small GTPases of the Rho family are involved in the regulation of a variety of cellular processes, such as the organization of the microfilamental net work, cell-cell contact and malignant transformation. To address the questi on of whether Rho proteins are involved in carcinogenesis in man, we compar ed their expression in tumors from colon, breast and lung with that of the corresponding normal tissue originating from the same patient. As shown by Rho-specific P-32-ADP-ribosylation, as well as Western-blot analysis, the a mount of RhoA protein was largely increased in all 3 types of tumors tested . The most dramatic differences in the expression of Rho GTPases were obser ved in breast: tissue. All breast tumors analyzed showed high levels of Rho A, pac and Cdc42 proteins, whereas in the corresponding normal tissue these Rho proteins were hardly or not detectable. Progression of breast tumors f rom WHO grade I to grade III was accompanied by a significant average incre ase in RhoA protein. Overall, increase in the amount of Rho GTPases, in par ticular RhoA, appears to be a frequent event in different types of human tu mors, This supports the view that Rho GTPases are involved in human carcino genesis. (C) 1999 Wiley-Liss, Inc.