PAX3 in neuroblastoma: oncogenic potential, chemosensitivity and signalling pathways

Journal of Cellular and Molecular Medicine

Wen-Hui Fang¹  Qiuyu Wang²  Hong-Mei Li²  Mashud Ahmed²  Patricia Kumar² 

[1] Institute of Inflammation and Repair, Faculty of Medicine and Human Sciences, The University of Manchester, Manchester, UK;School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, UK

关键词: PAX3;    neuroblastoma;    RNA interference;    cellular functions;    microarray;    signalling pathway;   

DOI  :  10.1111/jcmm.12155

来源: Wiley

【 摘 要 】

Abstract

Transcription factor PAX3/Pax3 contributes to diverse cell lineages during embryonic development and is important in tumourigenesis. We found that PAX3 is re-expressed in neuroblastoma and malignant neuroblastic (N-type) neuroblastoma cells had significantly higher PAX3 protein expression than their benign substrate-adherent (S-type) counterparts. Knock-down of PAX3 expression by siRNA transfection resulted in persistent cell growth inhibition in both types of neuroblastoma cell, owing to G1 cell cycle arrest and progressive apoptosis. Inhibition of PAX3 expression significantly decreased the attachment of S-type SH-EP1 cells to extra-cellular matrix proteins, fibronectin, laminin and collagen IV. Migration and invasion of both neuroblastoma cell types were markedly reduced after PAX3 down-regulation. PAX3 knock-down significantly augmented the cytotoxic effect of chemotherapeutic agents, etoposide, vincristine and cisplatin, commonly used to treat neuroblastoma. Microarray analyses revealed that particularly signalling pathways involving cell cycle, apoptosis, cell adhesion, cytoskeletal remodelling and development were altered by PAX3 down-regulation. Changes in PAX3 downstream genes identified by microarray analyses were validated in 47 genes by quantitative PCR. These novel findings lead us to propose that PAX3 might contribute to oncogenic characteristics of neuroblastoma cells by regulating a variety of crucial signalling pathways.

【 授权许可】

CC BY   
© 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.