MAGE-A9 mRNA and protein expression in bladder cancer

✍ Scribed by Valérie Picard; Alain Bergeron; Hélène LaRue; Yves Fradet

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 362 KB
• Volume: 120
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22282

✦ Synopsis

Abstract

In a previous analysis, we showed that MAGE‐As were the most frequently expressed cancer‐testis antigens in human bladder tumours. Here, we further characterized by RT‐PCR the expression of this family of genes by analyzing specifically MAGE‐A3, ‐A4, ‐A8 and ‐A9 mRNAs in 46 bladder tumours and 10 normal urothelia. We found that they were expressed in 30, 33, 56 and 54% of tumours, respectively. Although MAGE‐A8 was the most frequent, its expression was low and was also found in most normal urothelia. The other MAGE‐A mRNAs were all tumour‐specific but MAGE‐A9 mRNA was expressed at a higher level and was two times more frequent in superficial than in invasive tumours. To study the expression of the protein, we produced 2 MAGE‐A9‐specific monoclonal antibodies (mAbs) presenting no cross‐reactivity with other MAGE‐A proteins. MAb 14A11, was used to analyse the expression of the antigen in testis and tumour samples by immunohistochemistry. In testis, MAGE‐A9 expression was restricted to primary spermatocytes. Most bladder tumours that expressed the MAGE‐A9 transcript were positive with mAb 14A11. Staining was heterogeneous but half of the tumours showed over 75% positive cells. Finally, we showed that treatment of bladder cancer cells with the methylation inhibitor, 5‐aza‐2′‐deoxycytidine, alone or in combination with the histone deacetylase inhibitors MS‐275 and 4‐phenylbutyrate could strongly induce the expression of MAGE‐A9. These results show that MAGE‐A9 is frequently expressed in superficial bladder cancer and could be a relevant target for immunotherapy or chemoimmunotherapy because its expression can be induced by chemotherapeutic drugs. © 2007 Wiley‐Liss, Inc.