[The role of actin alteration in the neoplastic transformation]

Alteration of cell shape, motility and membrane fluidity which result in the disorganized cell arrangement and orientation, uncontrolled cell growth, and abnormal response to the environment have been considered one of the most striking and universal phenotypes characteristics of neoplastic cells. Cytoplasmic actins, i.e., beta-and gamma-actin, are the major molecules of the cytoskeleton whose function is involved in maintaining and controlling cell morphology, motility and membrane fluidity. In fact, most transformed cells show abnormal and disorganized structure of actin cable network. Thus, it is conceivable that alteration of structure and function of actin or microfilament may lead the cells to express the transformed phenotypes. A new polypeptide recognized in a chemically transformed human fibroblast line was identified as a variant form of actin. mRNA coding for the variant actin was detected only in this particular transformed line. The size and cross-hybridizability with dictyostelium actin cDNA of mRNA coding for the variant actin and complete amino acid sequence of the variant actin indicate that the new variant actin is a mutated beta-actin. Only a single amino acid (glycine) at the position of 245 was substituted by aspartic acid. This substitution corresponds to a GC----AT transition, a point mutation. On the other hand, the highly malignant cell variant was isolated from the transformed line. The mutated beta-actin was further altered in this highly malignant subclone. This further altered mutant beta-actin showed more negative charge, rapid synthetic ratio, and short halflife in the cells. The incorporation of the mutated beta-actin into cytoskeleton was significantly reduced. A hypothesis on the role of alteration of actin and microfilament in oncogenic transformation is proposed.