Figure 4.

Heterogeneity in the induction of p53-responsive genes. (A) Time course of induction. The p21, Jun-B, Caveolin, and DR-5 genes were detectably induced by 3 hr after doxycycline withdrawal, whereas Gadd45 was induced 12 hr later. RNA was prepared from wtA cells at the indicated time points. (B) Induction by p53 adenoviruses. Class I genes included p21, Bax, Caveolin (Cav), DR5, Htk, and Gpc, whereas RTP, Jun-B, and Fas were class II genes, and thrombospondin (Tsp) was a class III gene. “W” and “M” refer to the adenoviruses expressing wt p53 and mutant p53, respectively. (C) Induction by chemotherapeutic agents. RNA from the indicated colorectal cancer cells lines treated with adriamycin (Adr) or 5-FU for 24 hr was analyzed. RNA from untreated cells was used as control (con). The expression of p21 was strongly induced by both drugs in both cell lines expressing wt p53 but was not induced in DLD-1 cells containing endogenous mutant p53 or in p53 KO cells. In contrast, Bax was induced by adriamycin but not by 5-FU. The induction of Bax by adriamycin was considerably stronger in the two lines with wt p53 than in DLD-1 or p53 KO cells. Another pattern was observed with Fas, in which little induction was observed in any of the lines studied.