Association of over-expressed TFDP1 with progression of hepatocellular carcinomas.
DP-1 is a heterodimerization partner for members of the E2F family of transcription factors; E2F/DP-1 regulates the expression of various cellular promoters, particularly gene products that are involved in the cell cycle. Our earlier studies identified the DP-1 gene ( TFDP1) as a probable target within a 13q34 amplicon that is frequently detected in hepatocellular carcinomas (HCC) and esophageal squamous-cell carcinomas. The aim of the present study was to investigate the clinicopathological significance of up-regulation of TFDP1 in HCC. We determined expression levels of TFDP1 and E2F1 in 41 primary HCCs by means of quantitative real-time reverse transcription-polymerase chain reactions, and looked for relationships between those data and various clinicopathological parameters. To assess transactivating activity of E2F1/DP-1, we also analyzed expression of ten putative transcriptional targets of this complex in HCCs. Using antisense oligonucleotides, we down-regulated TFDP1 in Hep3B, an HCC cell line that had shown overexpression of the gene, to examine the role of elevated TFDP1 expression in the growth of Hep3B cells. Elevated expression of TFDP1, but not E2F1, was associated significantly with large (> or =5 cm) tumor size (P=0.021). Expression levels of TFDP1 and E2F1 correlated with those of seven transcriptional targets ( TYMS, DHFR, PCNA, RRM1, CCNE1, CDC2, and MYBL2) that play important roles in the G1/S transition, and down-regulation of TFDP1 inhibited growth of Hep3B cells. In conclusion, overexpression of TFDP1 may contribute to progression of some HCCs by promoting growth of the tumor cells.
Yasui
Kohichiroh
K
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.|CREST, Japan Science and Technology Corporation, Kawaguchi, Japan.
Okamoto
Hiroyuki
H
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.|Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Arii
Shigeki
S
Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Inazawa
Johji
J
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. johinaz.cgen@mri.tmd.ac.jp.|CREST, Japan Science and Technology Corporation, Kawaguchi, Japan. johinaz.cgen@mri.tmd.ac.jp.
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002455:Cell Division; D002460:Cell Line; D002882:Chromosomes, Human, Pair 13; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D018797:Cell Cycle Proteins; D016376:Oligonucleotides, Antisense; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors