Journal of Carcinogenesis & Mutagenesis

Abstract

Loss of Melanoma-associated Antigen-A1 (MAGE-A1) Reverses Docetaxel Resistance and Increases Apoptosis via p53-independent Pathway in Gastric Cancer

Chen Xie, Natalia Liem, Foong Ying Wong, Fui Leng Yan and Wei Peng Yong

Melanoma Associated Antigen (MAGE)-encoding genes have been shown to be aberrantly expressed in various tumour types, and correlate with tumour progression and resistance to docetaxel. The objective of this study was to elucidate the regulatory mechanism underlying MAGE-A1 related docetaxel resistance in gastric cancer cells. Gastric cell lines with high docetaxel IC50 had higher expression of MAGE-A1 compared to cell lines with low docetaxel IC50 (p=0.0299). Knockdown of MAGE-A1 expression also resulted in an accumulation of cell populations in the G2/M phase of the cell cycle. An increased sensitivity to docetaxel was also observed in MAGE-A1 knockdown gastric cell line compared to its parental cell line. Loss of MAGE-A1 expression led to an increased expression of β-III tubulin, microtubule associated proteins, MAP4, and activation of apoptotic genes, p21, Bax and Bcl-2. Significant inverse correlation was observed between MAGE-A1 expression and its methylation in the gastric cancer cell lines. Collectively, our study demonstrated the expression of MAGE-A1 was regulated by methylation, and contributed to docetaxel sensitivity in gastric cancer cell lines through modulation of microtubules and proteins involving the apoptotic pathway.