title: Roles for rat hepatocyte malignant transforming factor (HMTF) in late stage of hepatocarcinogenesis.
abstract: In a previous study, to identify genes of importance for hepatocellular carcinogenesis, and especially for processes involved in malignant transformation, the authors investigated differences in gene expression between adenomas and carcinomas by DNA microarray. In the present study, the authors investigated AW434047, one of the sequences that was upregulated in carcinomas. The investigation led to the identification of a novel gene, which the authors named hepatocyte malignant transforming factor (HMTF), of unknown function whose expression was increased in hepatocellular carcinomas. Northern blot and in situ hybridization also demonstrated high levels of HMTF in rat hepatocellular carcinoma (HCC) cell lines, lymphocytes in the spleen, colon mucosal epithelia, spermatocytes, and granule cells of the hippocampus. Reduction of HMTF by RNA interference (RNAi) in N1 cells, an HCC cell line, caused suppression of cell proliferation, invasion, and migration. Suppression of proliferation appeared to be due to cell cycle arrest without increased apoptosis. Decreased HMTF expression resulted in down-regulation of STAT3, PCNA, and cyclin D1 and upregulation of p27. These results suggest that HMTF is a new marker for rat HCC and is involved in HCC cell proliferation and may also be linked to cell proliferation in the spleen, colon, brain, and testis.
authors.affiliation: Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takeshita
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering