Induction of anchorage independent growth and serum resistance in immortalized human bronchial 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 difficult to assess in view of the large number of other cellular changes that also occur. In this study, we transfected the SV40-immortalized human bronchial epithelial cell line, BEAS-2B, with human wild-type beta or gamma actin gene expression plasmids to induce cytoskeletal changes and to determine whether this was associated with altered cellular growth properties. Cells expressing the exogenous full-length actin genes 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 resistance to the normal growth inhibitory effects of fetal bovine serum. These phenotypic changes correlated with changes in actin mRNA levels, but not with changes in actin protein levels. The phenotypically altered cells were not tumorigenic when injected subcutaneously in athymic nude mice, and they retained the ability to suppress the tumorigenic potential of a lung carcinoma cell line, HuT-292. Therefore, alteration of the cytoskeleton of immortalized human bronchial epithelial cells resulted in the acquisition of some properties commonly found in malignant cells, but did not result in tumorigenicity.
De Silva
R
R
Cancer Research Unit, Children's Medical Research Institute, Westmead, Sydney, N.S.W., Australia.
Englezou
A
A
Schevzov
G
G
Gerwin
B I
BI
Harris
C C
CC
Gunning
P
P
Reddel
R R
RR
D000199:Actins / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology; D002448:Cell Adhesion; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D003470:Culture Media; D003599:Cytoskeleton / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000209:etiology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine; D014162:Transfection
D000199:Actins; D003470:Culture Media; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine