title: ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry.
abstract: Using high-density oligonucleotide microarrays, we investigated DNA copy-number aberrations in cell lines derived from hepatocellular carcinomas (HCCs) and detected a novel amplification at 17p11. To identify the target of amplification at 17p11, we defined the extent of the amplicon and examined HCC cell lines for expression of all seven genes in the 750-kb commonly amplified region. Mitogen-activated protein kinase (MAPK) 7, which encodes extracellular-regulated protein kinase (ERK) 5, was overexpressed in cell lines in which the gene was amplified. An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Downregulation of MAPK7 by small interfering RNA suppressed the growth of SNU449 cells, the HCC cell line with the greatest amplification and overexpression of MAPK7. ERK5, phosphorylated during the G2/M phases of the cell cycle, regulated entry into mitosis in SNU449 cells. In conclusion, our results suggest that MAPK7 is likely the target of 17p11 amplification and that the ERK5 protein product of MAPK7 promotes the growth of HCC cells by regulating mitotic entry.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Keika
authors.initials: K
authors.lastname: Zen
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Kan
authors.initials: K
authors.lastname: Zen
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gen
authors.forename: Hironori
authors.initials: H
authors.lastname: Mitsuyoshi
authors.forename: Masahito
authors.initials: M
authors.lastname: Minami
authors.forename: Shoji
authors.initials: S
authors.lastname: Mitsufuji
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics* / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D008940:Mitotic Index; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000235:genetics; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7