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Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival.

Publication ,  Journal Article
Willett, CG; Smith, DI; Shridhar, V; Wang, MH; Emanuel, RL; Patidar, K; Graham, SA; Zhang, F; Hatch, V; Sugarbaker, DJ; Sunday, ME
Published in: J Clin Invest
June 15, 1997

Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung tumors develop in nitrosaminetreated hamsters, which we hypothesized might modulate epithelial cell phenotype by expressing gene(s) homologous to human chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase receptor, RON, is present and functional on many of these neuroendocrine tumors. In H835, a pulmonary carcinoid cell line, and H187, a SCLC cell line, HGFL/ MSP induced adhesion/flattening and apoptosis. Using viable cell counts to assess proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia. These observations suggest that HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung injury, which could influence the ultimate tumor cell phenotype.

Duke Scholars

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

June 15, 1997

Volume

99

Issue

12

Start / End Page

2979 / 2991

Location

United States

Related Subject Headings

  • Sequence Homology
  • Receptors, Cell Surface
  • Receptor Protein-Tyrosine Kinases
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Mesocricetus
  • Lung Neoplasms
  • Lung Diseases
  • Immunology
  • Humans
 

Citation

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Willett, C. G., Smith, D. I., Shridhar, V., Wang, M. H., Emanuel, R. L., Patidar, K., … Sunday, M. E. (1997). Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival. J Clin Invest, 99(12), 2979–2991. https://doi.org/10.1172/JCI119493
Willett, C. G., D. I. Smith, V. Shridhar, M. H. Wang, R. L. Emanuel, K. Patidar, S. A. Graham, et al. “Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival.J Clin Invest 99, no. 12 (June 15, 1997): 2979–91. https://doi.org/10.1172/JCI119493.
Willett CG, Smith DI, Shridhar V, Wang MH, Emanuel RL, Patidar K, Graham SA, Zhang F, Hatch V, Sugarbaker DJ, Sunday ME. Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival. J Clin Invest. 1997 Jun 15;99(12):2979–2991.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

June 15, 1997

Volume

99

Issue

12

Start / End Page

2979 / 2991

Location

United States

Related Subject Headings

  • Sequence Homology
  • Receptors, Cell Surface
  • Receptor Protein-Tyrosine Kinases
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Mesocricetus
  • Lung Neoplasms
  • Lung Diseases
  • Immunology
  • Humans