Changes in expression of members of the fos and jun families and myc network during terminal differentiation of human keratinocytes.

Normal human epidermal keratinocytes are induced to undergo terminal differentiation when disaggregated and placed in suspension: commitment occurs at about 5 h and overt differentiation by 24 h. In contrast, the squamous cell carcinoma line SCC12B2 does not initiate terminal differentiation until 75 h in suspension and the ndk strain of keratinocytes undergoes growth arrest but does not differentiate at all. In order to identify genes that may regulate terminal differentiation we have examined mRNA levels of members of the fos and jun gene families and myc gene network in suspension cultures of normal keratinocytes, SCC12B2 and ndk. The major changes observed were an up-regulation of c-Fos and Fra-1 and a decrease in c-Myc at the time of commitment, followed by an increase in Mad, Mxi1, Fra-2 and JunB expression at the onset of differentiation. The sequence of events shows a striking similarity to that which occurs during myeloid differentiation and suggests a role for AP-1 complexes and Myc and Mad complexes in regulating keratinocyte differentiation.