title: PNAS-4 expression and its relationship to p53 in colorectal cancer.
abstract: 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.
authors.affiliation: Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Keling
authors.initials: K
authors.lastname: Chen
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D019759:Carbon-Nitrogen Lyases; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D019759:Carbon-Nitrogen Lyases; C000604991:DESI2 protein, human