Reference SummaryStearman RS, Am J Pathol 2005 Dec;167(6):1763-75

Title

 Analysis of Orthologous Gene Expression between Human Pulmonary Adenocarcinoma and a Carcinogen-Induced Murine Model.

Authors

 Stearman RS; Dwyer-Nield L; Zerbe L; Blaine SA; Chan Z; Bunn PA Jr; Johnson GL; Hirsch FR; Merrick DT; Franklin WA; Baron AE; Keith RL; Nemenoff RA; Malkinson AM; Geraci MW

Journal

 Am J Pathol

Volume

 167

Issue

 6

Year

 2005

Pages

 1763-75

Abstract

 Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer, and its absolute incidence is increasing dramatically. Compared to human lung AC, the A/J mouse-urethane model exhibits similar histological appearance and molecular changes. We examined the gene expression profiles of human and murine lung tissues (normal or AC) and compared the two species' datasets after aligning approximately 7500 orthologous genes. A list of 409 gene classifiers (P value <0.0001), common to both species (joint classifiers), showed significant, positive correlation in expression levels between the two species. A number of previously reported expression changes were recapitulated in both species, such as changes in glycolytic enzymes and cell-cycle proteins. Unexpectedly, joint classifiers in angiogenesis were uniformly down-regulated in tumor tissues. The eicosanoid pathway enzymes prostacyclin synthase (PGIS) and inducible prostaglandin E(2) synthase (PGES) were joint classifiers that showed opposite effects in lung AC (PGIS down-regulated; PGES up-regulated). Finally, tissue microarrays identified the same protein expression pattern for PGIS and PGES in 108 different non-small cell lung cancer biopsies, and the detection of PGIS had statistically significant prognostic value in patient survival. Thus, the A/J mouse-urethane model reflects significant molecular details of human lung AC, and comparison of changes in orthologous gene expression may provide novel insights into lung carcinogenesis.

Links

 J:103641 – MGI References
16314486 – National Library of Medicine/PubMed

Strain Notes

Strain Note
A/J These mice were purchased from the Jackson Laboratory.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
A/J Lung adenocarcinoma
  • urethane (ethyl carbamate)
 Lung

observed
A/J Lung adenoma
  • urethane (ethyl carbamate)
 Lung

observed
A/J Lung normal tissue (control)
  • urethane (ethyl carbamate)
 Lung

not applicable