Retinoic Acid Induces the Expression of Alkaline Phosphatase in PI9

Retinoic acid (RA), the natural acid derivative of vitamin A, can induce the differentiation of some cell lines, such as the murine P19 teratocarcinoma cell line. RA can alter the expression of specific genes and the level of the corresponding protein. This report describes the effect of RA on the level of the alkaline phosphatase (ALP) mRNA and protein in P19 teratocarcinoma cells. RA caused a rapid, dose-dependent, and protein synthesis-dependent induction of ALP activity. The increased enzyme activity was detected 4 h after initiation of treatment and maximum induction of ALP activity required 48 h of RA exposure. Increased enzymatic activity was coincidental with increased levels of both a 67-kDa ALP protein and ALP mRNA. By Northern (RNA) blot analysis the increase of a 2.7-kilobase ALP mRNA was observed within 3 h of RA treatment. The RA-induced enhanced ALP mRNA level did not appear to be mainly due to the stabilization of preexisting mRNA, but rather to an increase in transcription of the ALP gene.