title: Increased expression of the LGALS3 (galectin 3) gene in human non-small-cell lung cancer.
abstract: Patients with lung cancer have a poor prognosis because of the high metastatic potential of the neoplasm. Therefore, identifying new molecular targets for anti-metastatic therapy is very important. To identify novel key factors of tumor metastasis in lung cancer, we established the gene expression profiles of two adenocarcinoma cell line variants, PC9/f9 and PC9/f14, by use of genome-wide human cDNA microarray analysis and comparing these profiles with that of the parental cell line, PC9. The PC9/f9 and PC9/f14 cell lines were selected for analysis because of their high metastatic potential. We identified five genes in the highly metastatic cell lines that showed a significantly enhanced or reduced expression and that had not been reported to be involved in metastasis of lung cancer. One of the overexpressed genes that was identified encoded the beta-galactoside-binding protein LGALS3 (Galectin 3). LGALS3 has been reported to be overexpressed in a variety of human cancers, but not in lung cancer, and to be involved in tumor metastasis. We examined the expression of LGALS3 by use of real-time quantitative reverse transcription-polymerase chain reaction in 38 lung cancer cell lines and in tumor tissue obtained by thoracoscopic biopsy. A population (10/30) of the non-small-cell lung cancers examined was found to overexpress the LGALS3 gene at levels three times higher than those of normal epithelial cells. In contrast, all small-cell lung cancers either failed to express the gene or expressed it at a very low level. The mean of the relative expression of the LGALS3 gene in non-small-cell lung cancer (3.065 +/- 3.976) was significantly higher than those of small-cell lung cancer (0.02 +/- 0.03) (P < 0.025). This is the first report of alterations of LGALS3 gene expression in lung cancer. These results, together with the previous reports on Galectin 3 function, suggest that Galectin 3 may play a role in the process of metastasis in non-small-cell lung cancer that overexpresses Galectin 3, but not in small-cell cancer. Accordingly, LGALS3 may be a phenotypic marker that excludes small-cell lung cancer and may represent a novel target molecule in non-small-cell lung cancer therapy.
authors.affiliation: Fourth Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hosoya
authors.forename: Eriko
authors.initials: E
authors.lastname: Komaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosomi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okano
authors.forename: Kiyosi
authors.initials: K
authors.lastname: Takenaka
authors.forename: Kuniko
authors.initials: K
authors.lastname: Matuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Seike
authors.forename: Kazutsugu
authors.initials: K
authors.lastname: Uematsu
authors.forename: Suguru
authors.initials: S
authors.lastname: Hibino
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D037502:Galectin 3 / Q000096:biosynthesis* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D037502:Galectin 3