Mouse Balb/c3T3 cell mutant with low epidermal growth factor receptor activity: Induction of stable anchorage‐independent growth by transforming growth factor β

Abstract

A mutant clone was originally isolated as a clone resistant to Na+/K+ ionophoric antibiotic monensin from mouse Balbk3T3 cells. was found to show low receptor-endocytosis activity for epidermal growth factor (ECF): binding activity for ECF in was less than one tenth of that in Balbk3T3. Anchorage-independent growth of MO-5 was compared to that of BaIbk313 when assayed by colony formation capacity in soft agar. Coadministration of EGF and TGF-@ efficiently enhanced anchorage-independent growth of normal rat kidney (NRK) cells, but neither factor alone was competent to promote the anchorage-independent growth. The frequency of colonies appearing in soft agar of or BaIbk3T3 was significantly enhanced by TCF-@ while EGF did not further enhance that of or BaIbk3T3. Colonies of BaIbk3T3 formed in soft agar in the presence of TCF-@ showed low colony formation capacity in soft agar in the absence of TCF-@. Colonies of formed by TGF-@ in soft agar, however, showed high colony formation capacity in soft agar in the absence of TGF-@. Pretreatment of with TGF-@ induced secretion of TCF-@-like activity from the cells, while the treatment of Balb/ c3T3 did not induce the secretion of a significant amount of TGF-@-like activity. The loss of ECF-receptor activity in the stable expression and maintenance of the "transformed" phenotype in MO-5 is discussed.