The PAX5 oncogene is expressed in N-type neuroblastoma cells and increases tumorigenicity of a S-type cell line.
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.
Baumann Kubetzko
Florian B
FB
Forschungslabor Molekulare Onkologie, Klinik und Poliklinik für Onkologie, Universitaetsspital Zurich, Haeldeliweg 4, CH-8044 Zurich, Switzerland.
Di Paolo
Claudio
C
Maag
Charlotte
C
Meier
Roland
R
Schäfer
Beat W
BW
Betts
David R
DR
Stahel
Rolf A
RA
Himmelmann
Andreas
A
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009447:Neuroblastoma / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D051757:PAX5 Transcription Factor; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors