title: Establishment of an immortalized cell line from a precancerous lesion of lung adenocarcinoma, and genes highly expressed in the early stages of lung adenocarcinoma development.
abstract: Atypical adenomatous hyperplasia (AAH) is classified as a precancerous lesion of lung adenocarcinoma. We established an immortalized AAH cell line (PL16T) and a human non-neoplastic bronchial epithelial cell line (PL16B) from the same patient by transfection with the gene for SV40 large T antigen. The expression profile of PL16T was compared with that of PL16B by the suppression subtractive hybridization method. From 704 selectively hybridized clones, we finally selected 25 fragments of mRNA that showed transcription levels more than three times higher in PL16T than in PL16B. Thirteen (52%) and eight (32%) of them encoded tumor-associated calcium signal transducer 2 (TACSTD2) and S100 calcium binding protein A2 (S100A2), respectively. The high transcription of TACSTD2 and S100A2 in PL16T was confirmed by in situ hybridization. In normal lung tissue, both TACSTD2 and S100A2 were expressed at very low levels, but seven and five of 14 AAH were positive for TACSTD2 and S100A2, respectively. The frequency of TACSTD2 positivity was increased in 16 of 22 bronchioloalveolar carcinomas (BAC) and adenocarcinoma with mixed subtype with BAC component (mixed BAC). Positivity for S100A2 occurred in four of 22 BAC and mixed BAC. The abnormal transcription of TACSTD2 and S100A2 are thought to be unique molecular markers of the preinvasive stage of lung adenocarcinoma.
authors.affiliation: Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Shimada
authors.forename: Junko
authors.initials: J
authors.lastname: Kano
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishiyama
authors.forename: Chigusa
authors.initials: C
authors.lastname: Okubo
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Iijima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Morishita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Minami
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Inadome
authors.forename: Yujian
authors.initials: Y
authors.lastname: Shu
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sugita
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002630:Chemotactic Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D009418:S100 Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D009418:S100 Proteins; C098997:S100A2 protein, human; C499380:TACSTD2 protein, human