The comparative effects of tumor-related agents on developmental marker expression in presumptive myoblasts and myotubes.

The effect of a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on differentiation marker expression in skeletal myotubes and their immediate progenitors, presumptive myoblasts (PMbs), was investigated. The markers employed included the K-isozyme of pyruvate kinase (PK-K) and a newly characterized phosphoprotein (pp(65;4.5)), which are both normally concentrated in PMbs, and the M-isozyme of pyruvate kinase (PK-M) and phosphorylated derivatives of alpha- and beta-tropomyosin (pT), which are normally concentrated in myotubes. PMbs treated with TPA for 3, 6 or 10 days continued to express PK-K and pp(65;4.5), and did not express PK-M or pT at detectable levels. Myotubes which were treated for 3 or 6 days were inhibited in their expression of PK-M and pT, but were not stimulated in their expression of PK-K or pp(65;4.5). The effects of TPA were reversible upon discontinuation of treatment. In parallel experiments, where pp(65;4.5) and pT were monitored, infection with Rous sarcoma virus (RSV) had similar effects. The data suggest that TPA treatment and RSV transformation do not alter the state of differentiation of target cells per se but, in the case of myotubes, do suppress the expression of that state.