INDUCTION OF ANCHORAGE-INDEPENDENT GROWTH AND SERUM RESISTANCE IN IMMORTALIZED HUMAN BRONCHLAL EPITHELIAL-CELLS BY ALTERATION OF THE CYTOSKELETON

Malignant transformation is frequently accompanied by obvious changes in cytoarchitecture, but the importance of these changes has been diff icult to assess in view of the large number of other cellular changes that also occur. In this study, we transfected the SV40-immortalized h uman bronchial epithelial cell line, BEAS-2B, with human wild-type bet a or gamma actin gene expression plasmids to induce cytoskeletal chang es and to determine whether this was associated with altered cellular growth properties. Cells expressing the exogenous full-length actin ge nes underwent a fibroblastoid change in morphology which was reflected in changes in their pattern of actin cable organization, and acquired both the ability to grow under anchorage-independent conditions and r esistance to the normal growth inhibitory effects of fetal bovine seru m. These phenotypic changes correlated with changes in actin mRNA leve ls, but not with changes in actin protein levels. The phenotypically a ltered cells were not tumorigenic when injected subcutaneously in athy mic nude mice, and they retained the ability to suppress the tumorigen ic potential of a lung carcinoma cell line, HuT-292. Therefore, altera tion of the cytoskeleton of immortalized human bronchial epithelial ce lls resulted in the acquisition of some properties commonly found in m alignant cells, but did not result in tumorigenicity.