Fig. 5. KLF11 suppresses oncogene-mediated transformation in an mSin3A-dependent manner. (A) The overexpression of KLF11 in NIH 3T3 cells significantly reduces the number of foci induced by a mutant H-ras when compared with cells transfected with H-ras alone. (B) This inhibition of the ras-mediated anchorage-dependent growth was not due to decreased H-ras expression caused by co-transfection with KLF11, as shown by northern blot analysis. (C) Cells transfected with H-ras alone had ∼8-fold differences compared with those cotransfected with H-ras and KLF11 in the number of foci. (D and E) KLF11 inhibits not only ras-mediated, anchorage-dependent growth, but also anchorage-dependent growth induced by other well characterized oncogenes such as Gα12, K-ras A, K-ras B and middleT, compared with cells transfected with oncogene alone. Taken together, these results indicate that KLF11 can function as a potent suppressor of anchorage-dependent cell growth induced by several well characterized oncogenes in vitro. (F) KLF11 deletion mutants that lack SID or contain only the zinc finger domain are not able to inhibit proliferation. Control western blot shows that the expression of the mutants is similar to the full length KLF11. (G) The KLF11 full-length protein can inhibit anchorage-dependent growth induced by H-ras, whereas the deletion mutants that lack SID or contains only the zinc finger can not. (H) KLF11 is strongly suppressed in tumors derived from pancreas, breast, kidney, lung, ovary, colon and stomach when compared with corresponding normal cDNA. The results shown are representative examples of the tumors examined.