Journal Article

The <i>PAX5</i> oncogene is expressed in N-type neuroblastoma cells and increases tumorigenicity of a S-type cell line

Florian B. Baumann Kubetzko, Claudio di Paolo, Charlotte Maag, Roland Meier, Beat W. Schäfer, David R. Betts, Rolf A. Stahel and Andreas Himmelmann

in Carcinogenesis

Volume 25, issue 10, pages 1839-1846
Published in print October 2004 | ISSN: 0143-3334
Published online October 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh190
The PAX5 oncogene is expressed in N-type neuroblastoma cells and increases tumorigenicity of a S-type cell line

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Neuroblastoma is a neural crest-derived neoplasm of infancy with poor outcome in patients with advanced disease. The oncogenic transcription factor PAX5 is an important developmental regulator and is implicated in the pathogenesis of several malignancies. Screening of neuroblastoma cell lines revealed PAX5 expression in a malignant subset of neuroblastoma cells, so-called ‘N-type’ cells, but not in the more benign ‘S-type’ neuroblastoma cells. PAX5 expression was also detected in small cell lung cancer, an aggressive tumor of neural crest origin. Based on this observation we hypothesized that there could be a relationship between PAX5 expression and the more malignant phenotype of N-type cells. Stable PAX5 expression was established in several clones of the S-type cell line CA-2E. A noticeable difference in morphology of these transfectants was observed and there was also a significant increase in the proliferation rate. Moreover, PAX5 expressing clones gained the ability to form colonies in a soft agar assay, a marker of tumorigenicity. Down-regulation of PAX5 in several N-type cell lines and one small cell lung cancer cell line utilizing small interfering RNA resulted in a significant decrease in growth rate. Taken together we propose PAX5 as an important factor for the maintenance of the proliferative and tumorigenic phenotype of neuroblastoma. Our data, together with a recent study on the role of PAX genes in cancer suggest that PAX5 and other PAX transcription factors might be valuable targets for cancer therapy.

Keywords: MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; scRNA, scrambled control; siRNA, small interfering RNA

Journal Article.  5694 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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