TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS NUCLEOSOMAL FRAGMENTATION IN HUMAN KERATINOCYTES FOLLOWING LOSS OF ADHESION

We have investigated the role of transforming growth factor-beta 1 (TG F-beta 1) in suspension-induced programmed cell death of cultured huma n keratinocytes. Suspension of keratinocytes in semisolid medium induc es TGF-beta 1 mRNA levels and synthesis of bioactive TGF-beta 1 protei n. Concomitant with the suspension-induced increase in secreted TGF-be ta 1 levels, steady state mRNA levels for c-myc are decreased. Both ex ogenously added and endogenously produced TGF-beta 1 attenuate suspens ion-induced nucleosomal fragmentation in keratinocytes. We propose tha t TGF-beta 1 may function to protect keratinocytes from DNA fragmentat ion following loss of cell-substratum and/or cell-cell contact. Taken together, our findings suggest that loss of cell-substratum and/or cel l-cell adhesion is an important component of an apoptotic signal trans duction cascade regulated by TGF-beta 1 in normal human stratified squ amous epithelia.