Abstract
BackgroundSeveral studies have shown that NDRG2 mRNA is down-regulated or undetectable in various human cancers and cancer cell-lines. Although the function of NDRG2 is currently unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas, gastric cancer and hepatocellular carcinomas. Furthermore, in vitro studies have revealed that over-expression of NDRG2 in cell-lines causes a significant reduction in their growth. The aim of this study was to examine levels of NDRG2 mRNA in several human cancers, with focus on breast cancer, by examining affected and normal tissue.MethodsBy labelling a human Cancer Profiling Array with a radioactive probe against NDRG2, we evaluated the level of NDRG2 mRNA in 154 paired normal and tumor samples encompassing 19 different human cancers. Furthermore, we used quantitative real-time RT-PCR to quantify the levels of NDRG2 and MYC mRNA in thyroid gland cancer and breast cancer, using a distinct set of normal and tumor samples.ResultsFrom the Cancer Profiling Array, we saw that the level of NDRG2 mRNA was reduced by at least 2-fold in almost a third of the tumor samples, compared to the normal counterpart, and we observed a marked decreased level in colon, cervix, thyroid gland and testis. However, a Benjamini-Hochberg correction showed that none of the tissues showed a significant reduction in NDRG2 mRNA expression in tumor tissue compared to normal tissue. Using quantitative RT-PCR, we observed a significant reduction in the level of NDRG2 mRNA in a distinct set of tumor samples from both thyroid gland cancer (p = 0.02) and breast cancer (p = 0.004), compared with normal tissue. MYC mRNA was not significantly altered in breast cancer or in thyroid gland cancer, compared with normal tissue. In thyroid gland, no correlation was found between MYC and NDRG2 mRNA levels, but in breast tissue we found a weakly significant correlation with a positive r-value in both normal and tumor tissues, suggesting that MYC and NDRG2 mRNA are regulated together.ConclusionExpression of NDRG2 mRNA is reduced in many different human cancers. Using quantitative RT-PCR, we have verified a reduction in thyroid cancer and shown, for the first time, that NDRG2 mRNA is statistically significantly down-regulated in breast cancer. Furthermore, our observations indicate that other tissues such as cervix and testis can have lower levels of NDRG2 mRNA in tumor tissue compared to normal tissue.
Highlights
Several studies have shown that N-Myc Downstream RegulatedGene 2 (NDRG2) mRNA is down-regulated or undetectable in various human cancers and cancer cell-lines
Expression profile of NDRG2 in human cancers By hybridising a CPA with a radioactive labelled probe it was possible to examine the levels of NDRG2 mRNA in 19 different human cancers, distributed as 154 paired tissue samples, and 9 different cell lines
Using quantitative RT-PCR, we demonstrated that NDRG2 mRNA levels were statistically significantly reduced in breast cancer tissue when compared to normal tissue
Summary
Several studies have shown that NDRG2 mRNA is down-regulated or undetectable in various human cancers and cancer cell-lines. The transformation of normal cells into cancer cells is generally believed to rely on genetic or epigenetic changes in the genome These changes often activate oncogenes and/or inactivate tumor suppressor genes. Elevated expression of NDRG2 in tumors correlates with an improved prognosis in gastric cancer, high-grade glioma and hepatocellular carcinomas [2,6,7]. Several in vitro studies have demonstrated a reduced cell growth when NDRG2 was over-expressed in cell-lines lacking endogenous expression [5,8]. These data suggest that NDRG2 might have a role in suppressing carcinogenesis
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