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LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung

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Abstract

No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription–polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0±8.1) than in normal lung tissues (1.0±0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.

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Acknowledgements

We thank Dr. Robert Timms for correcting the English version of the manuscript. The anti-LAT1 antibody was supplied by Kumamoto Immunochemical Laboratory, Transgenic.

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Authors and Affiliations

  1. Department of Pathology, National Defense Medical College, Tokorozawa, 359-8513, Japan

    Kuniaki Nakanishi, Sadayuki Hiroi, Susumu Tominaga & Toshiaki Kawai

  2. Department of Physiology, National Defense Medical College, Tokorozawa, 359-8513, Japan

    Hirotaka Matsuo

  3. Department of Pharmacology and Toxicology, School of Medicine, Kyorin University, Tokyo, 181-8611, Japan

    Yoshikatsu Kanai & Hitoshi Endou

  4. Division of Diagnostic Pathology, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Makio Mukai

  5. Department of Pathology, School of Medicine, Keio University, Tokyo, 160-8582, Japan

    Eiji Ikeda

  6. Department of Surgery, National Defense Medical College, Tokorozawa, 359-8513, Japan

    Yuichi Ozeki

  7. Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, 359-8513, Japan

    Shinsuke Aida

Authors
  1. Kuniaki Nakanishi
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  2. Hirotaka Matsuo
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  3. Yoshikatsu Kanai
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  4. Hitoshi Endou
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  5. Sadayuki Hiroi
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  6. Susumu Tominaga
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  7. Makio Mukai
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  8. Eiji Ikeda
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  9. Yuichi Ozeki
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  10. Shinsuke Aida
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  11. Toshiaki Kawai
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Correspondence to Kuniaki Nakanishi.

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Nakanishi, K., Matsuo, H., Kanai, Y. et al. LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung. Virchows Arch 448, 142–150 (2006). https://doi.org/10.1007/s00428-005-0063-7

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  • DOI: https://doi.org/10.1007/s00428-005-0063-7

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