PNAS-
4 is a novel pro-apoptotic protein activated during the early response to DNA damage; however, the molecular mechanisms and
pathways regulating
PNAS-
4 expression in tumors are not well understood. We hypothesized that
PNAS-
4 is a p53 down-stream target gene and designed this study. We searched online for putative p53-binding sites in the entire
PNAS-
4 gene and did not find any corresponding information. In HCT116 colon cancer cells, after being transfected with small interfering
RNA to silence p53, the expressions of
PNAS-
4 and other known p53 target gene (Apaf1, Bax, Fas and Dr5) were determined by real-time PCR. We found that
PNAS-
4 was up-regulated while Apaf1, Bax, Fas and Dr5 were down-regulated. We then examined the expression of
PNAS-
4 and p53 mutation in colorectal cancer patients.
PNAS-
4 expressed both in colorectal cancers and normal tissues, but compared with paired control,
PNAS-
4 was up-regulated in cancers (
P = 0.018).
PNAS-
4 overexpression ratios were correlated to the p53 mutant status (
P = 0.001). The mean
PNAS-
4 expression levels of p53 mutant homozygote group and heterozygote group were higher than that of p53 wild type group (
P = 0.013). The expression ratios of
PNAS-
4 (every sample in relative to its paired normal mucosa) were different between negative lymph node metastasis (66% up-regulated,
34% down-regulated) and positive metastasis (42% up-regulated, 58% down-regulated). Taken together, these findings suggested
that
PNAS-
4 was not a p53 target, but overexpression of
PNAS-
4 was correlated to p53 inactivity in colorectal cancer.
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