Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620.
Despite the wide use of 5-fluorouracil (5-FU) for colon cancer, the genes regulating its cytotoxic effect are poorly understood. We used a high-density oligonucleotide microarray representing approximately 7000 genes to determine changes in gene expression caused by 5-FU treatment in the colon cancer cell line, SW620. The microarray showed that the most strongly up-regulated gene by 5-FU was vitamin D3 up-regulated protein 1 (VDUP1), an interesting stress response gene, which was originally reported as a vitamin D3 inducible gene in HL-60. TaqMan RT-PCR assay confirmed that VDUP1 gene expression was significantly increased after 24 h of 5-FU treatment compared with untreated control (p<0.01). Moreover, the expression of vitamin D3 receptor, thymidylate synthase (TS), and E2F1 did not change within 24 h of 5-FU treatment, suggesting a different gene-regulatory pathway from that of VDUP1. Recent studies have gradually clarified the potential role of VDUP1 via interaction with TRX in an anti-tumor effect. Therefore, VDUP1 not only may be induced by stress response as a result of 5-FU cytotoxicity, but may also play a key role in 5-FU cytotoxicity in colon cancers. Our experiment using a microarray and TaqMan RT-PCR assay, together with previous reports, provides new insight into a potential mechanism of 5-FU cytotoxicity.
Takahashi
Yasuo
Y
Medical Research Center, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan. yasuot@med.nihon-u.ac.jp
Nagata
Toshihito
T
Ishii
Yukimoto
Y
Ikarashi
Masahito
M
Ishikawa
Koichi
K
Asai
Satoshi
S
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005472:Fluorouracil / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013879:Thioredoxins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D002352:Carrier Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C486715:TXNIP protein, human; D013879:Thioredoxins; D005472:Fluorouracil