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Differential Gene Expression in Human Lung Adenocarcinomas and Squamous Cell Carcinomas¹

Department of Pathology, Medical College of Ohio, Toledo, Ohio 43614 [A. L. M-S., C. F. N., M. Y.]; School of Public Health [G. D. S.] and Division of Human Cancer Genetics [M. Y.], The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210; and Chemoprevention Branch, National Cancer Institute, Bethesda, Maryland 20892 [R. A. L.]

Purpose: Differential cDNA library screening was performed on 7 human lung adenocarcinomas and 7 human lung squamous cell carcinomas and their corresponding adjacent normal tissues using a human lung cDNA library constructed from the normal bronchoalveolar cells of a 72-year-old male smoker.

Experimental Design: Of the 2758 clones that were differentially expressed between normal and tumor tissues in the preliminary cDNA library screening analysis, 1163 clones were confirmed by dot blot, revealing a confirmation rate of >40%. DNA of confirmed clones was sequenced and was subjected to GenBank Blast searches. RNA expression levels were then individually analyzed by semiquantitative reverse transcription-PCR.

Results: Ninety-two genes/sequences were differentially expressed in adenocarcinomas and/or squamous cell carcinomas compared with their corresponding normal tissues. Several genes were underexpressed by at least 50% in both tumor types such as c-fos, decorin, -2-macroglobulin, platelet endothelial cell adhesion molecule 1, EGR1, and fibronectin. Ribosomal protein S3 was underexpressed only in squamous cell carcinomas, whereas expression of hepatocyte growth factor activator inhibitor type 2, ubiquitin-conjugating enzyme UBC9, and clone 333E23 on chromosome Xq21.1 were altered only in adenocarcinomas. Several genes discovered recently of which the functions are unknown, such as KIAA0728 and KIAA0425, were also differentially expressed in both adenocarcinomas and squamous cell carcinomas of the lung.

Conclusions: Many of these known and novel genes may be involved in human lung tumorigenesis; therefore, additional characterization is warranted and will be beneficial to the understanding of this deadly disease.

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