N-Myc downstream regulated gene 2 may indicate the therapeutic sensitivity of human epidermal growth factor receptor-2 positive breast cancer to Herceptin

Abstract

Objective To investigate the expression of N-Myc downstream regulated gene 2 (NDRG2) in human epidermalgrowth factor receptor-2 (Her-2) positive breast cancer and the impact of sensitivity to Herceptin. Methods Western blotting was used to detect the difference of NDRG2 expression in breast cancer cells with different molecular typing. We excavated the expression of NDRG2 in different subtype of breast cancer and the relevance between NDRG2 and Her-2 by the Cancer Genome Atlas (TCGA) database, analyzed the immunohistochemistry (IHC) of Her-2+ breast cancer diagnosed in Xijing Hospital from January 2015 to January 2017, explored the expression of NDRG2 in Her-2+ breast cancer andthe adjacent normal tissues. To construct a breast cancer cell line with over-expression of NDRG2 and observe the sensitivity of Herceptin. Results Western blotting shows that the expression of NDRG2 in Her-2+ breast cancer is the lowest compared with ER+ breast cancerand triple negative breast cancer, respectively are 2.21±0.93 and 1.78±0.79, 6.31±1.15, 5.84±1.50. TCGA database presents that expression of NDRG2 in luminal, Her-2+ and TNBC breast cancer is lower than normal tissue, the median expressionrespectively are 42.378, 28.912, 96.163, 319.652, among them, the expression of NDRG2 in Her-2+ breast canceris the lowest, P<0.05. In breast cancer tissues, NDRG2 expression decreased with the amplification of Her-2 (27.814 vs. 10.711, P<0.01). IHC showed that the expression of NDRG2 in Her-2+ breast cancer was lower than the adjacent normal tissues (31.25% vs. 75.00%, P<0.01). Upregulation of NDRG2 in Her-2+ breast cancer can improve the sensitivity to Herceptin, inhibit proliferation (0.37±0.06 vs. 0.16±0.03, P<0.05), and promote apoptosis [(4.07±1.16)% vs. (25.91±3.64)%, P<0.01]. Conclusion The expression of NDRG2 was down-regulated in Her-2+ breast cancer, and its expression level can be indicated the therapeutic sensitivity of Her-2+ breast cancer to Herceptin. Key words: Breast cancer; N-Myc downstream regulated gene 2; Human epidermalgrowth factor receptor-2; Herceptin; Drug resistance