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

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. T...

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Veröffentlicht in:Cancer science 2005-10, Vol.96 (10), p.668-675
Hauptverfasser: Shimada, Aki, Kano, Junko, Ishiyama, Tadashi, Okubo, Chigusa, Iijima, Tatsuo, Morishita, Yukio, Minami, Yuko, Inadome, Yukinori, Shu, Yujian, Sugita, Shintaro, Takeuchi, Tomoyo, Noguchi, Masayuki
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container_end_page 675
container_issue 10
container_start_page 668
container_title Cancer science
container_volume 96
creator Shimada, Aki
Kano, Junko
Ishiyama, Tadashi
Okubo, Chigusa
Iijima, Tatsuo
Morishita, Yukio
Minami, Yuko
Inadome, Yukinori
Shu, Yujian
Sugita, Shintaro
Takeuchi, Tomoyo
Noguchi, Masayuki
description 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.(Cancer Sci 2005; 96: 668 – 675)
doi_str_mv 10.1111/j.1349-7006.2005.00100.x
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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. 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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. 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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.(Cancer Sci 2005; 96: 668 – 675)</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Pty</pub><pmid>16232198</pmid><doi>10.1111/j.1349-7006.2005.00100.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma - genetics
Adenocarcinoma - pathology
Antigens, Neoplasm - analysis
Antigens, Neoplasm - biosynthesis
Antigens, Neoplasm - genetics
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Cell Adhesion Molecules - analysis
Cell Adhesion Molecules - biosynthesis
Cell Adhesion Molecules - genetics
Chemotactic Factors - analysis
Chemotactic Factors - biosynthesis
Chemotactic Factors - genetics
Female
Gene Expression Profiling
Humans
Hyperplasia
Lung - pathology
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Medical sciences
Middle Aged
Neoplasm Staging
Nucleic Acid Hybridization
Original
Pneumology
Precancerous Conditions - genetics
Precancerous Conditions - pathology
S100 Proteins - analysis
S100 Proteins - biosynthesis
S100 Proteins - genetics
Simian virus 40
Tumor Cells, Cultured
Tumors
Tumors of the respiratory system and mediastinum
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
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