title: Expression of acidosis-dependent genes in human cancer nests.
abstract: Previous studies investigating cancer cells cultured at acidic pH have shown that the expression level of ~700 genes were more than two-fold higher than those of the cells cultured in alkaline medium at pH 7.5. The aim of the present study was to confirm whether these acidosis-induced genes are expressed in human cancer tissues. Therefore, 7 genes were selected from our previous study, which encoded interleukin 32 (IL-32), lysosomal H+transporting ATPase, V0 subunit d2 (ATP6V0D2), tumor necrosis factor receptor superfamily, member 9 (TNFRSF9), amphiregulin, schwannoma-derived growth factor (AREG), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ErbB3), PRR5-ARHGAP8 (LOC553158) and dimethylglycine dehydrogenase (DMGDH), and their expression was examined in human clinical specimens from patients with cancer. In addition, the expression of the gene encoding manganese superoxide dismutase (MnSOD) was examined. The specimens from patients with colon, stomach and renal cancer showed increasedMnSOD,IL-32, andTNFRSF9transcripts compared to those from non-tumorous regions of the same patients. Notably, an elevated expression ofATP6V0D2was found in the specimens from patients with stomach cancer, whereas the expression was decreased in those from patients with colon and renal cancer. The expression ofLOC553158was upregulated in colon and stomach cancer specimens. These results indicate that the investigation of gene expression under acidic conditions is useful for the development of novel cancer markers and/or chemotherapeutic targets.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fukamachi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Saito
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
keywords: acidic environments; gene expression; human cancer