title: Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-α secretion in gastric cancer.
abstract: We built an in-house oligonucleotide array on which 394 genes were selected based on our Serial Analysis of Gene Expression (SAGE) data and previously reported array data and listed several genes related to cancer progression. Among these, we focused on SEC11A, which encodes the SPC18 protein. SEC11A mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric cancer (GC) tissue samples. Expression and distribution of SPC18 protein were investigated by immunohistochemical analysis in two independent GC cohorts (Hiroshima cohort, n=99 and Chiba cohort, n=989). To determine the effect of SPC18 on cell viability and invasiveness in vitro, MTT and Boyden chamber invasion assays were performed. To evaluate the influence of SPC18 on cell growth in vivo, GC cells were injected into severe combined immunodeficiency mice. Levels of TGF-α and EGF in media from the GC cells were measured by enzyme-linked immunosorbent assay (ELISA). Studies in human tissue revealed overexpression of SEC11A mRNA in 40% of 42 GC samples by qRT-PCR. Immunohistochemical analysis of SPC18 revealed that 26 and 20% of GC cases were SPC18-positive in the Hiroshima and Chiba cohorts, respectively. In both cohorts, the Kaplan-Meier analysis showed poorer survival in SPC18-positive GC cases than in SPC18-negative GC cases. Forced expression of SPC18 activates GC cell growth in vitro and in vivo. The levels of TGF-α in culture media from GC cells were reduced by knockdown of SPC18. These results indicate that SPC18 contributes to malignant progression through promotion of TGF-α secretion in GC.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Oue
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takigahira
authors.affiliation: Pathology Division, and Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawano-Nagatsuma
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sentani
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Zarni Oo
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Uraoka
authors.affiliation: Division of Translational Research, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Pathology Division, and Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ochiai
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015999:Multivariate Analysis; D009368:Neoplasm Transplantation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D059467:Transcriptome; D016211:Transforming Growth Factor alpha / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: C587886:TGFA protein, human; D016211:Transforming Growth Factor alpha; D010447:Peptide Hydrolases; C000591565:SEC11A protein, human