Restoration of anchorage regulation in transformed cells by retinoic acid (RA) is independent of the presence of cytoplasmic RA-binding proteins.
In an attempt to analyse the cause-effect relationship between anchorage-independent growth (a property which correlates best with in vivo tumorigenicity) and a set of other common transformation-related properties, the effect of retinoic acid (RA) treatment on six unrelated transformed cell lines (including DNA tumor virus, retrovirus, and spontaneously transformed cells) were studied. The data show that the changes in morphology and cellular orientation in culture, loss of cell surface fibronectin, disruption of actin microfilaments, increased hexose uptake, loss of density-dependent growth, and decreased binding of EGF, properties which are often associated with oncogenic transformation of cells, are dissociable from one another and from anchorage-independent growth. RA appears to interfere with anchorage-independent growth of all the retrovirus and spontaneously transformed cell lines (responsive cells) that we examined; however, such treatment failed to inhibit anchorage-independent growth in both of the DNA tumor virus-transformed cell lines (non-responsive cells) that we used in the present study. The presence of RA-binding proteins in both responsive and non-responsive cells suggests that the mechanism of RA action for the inhibition of anchorage-independent growth in transformed cells may be independent of the presence of such cytoplasmic proteins. Finally, the present study clearly indicates that the use of RA treatment, like partial transformation mutants of oncogenic viruses, can be a novel approach in analysing the general mechanism by which transformed cells grow without anchorage.
D000199:Actins / Q000032:analysis; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018168:Receptors, Retinoic Acid; D014212:Tretinoin / Q000494:pharmacology*
D000199:Actins; D002352:Carrier Proteins; D005353:Fibronectins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D004815:Epidermal Growth Factor; D005947:Glucose