Expression profile of the N-myc Downstream Regulated Gene 2 (NDRG2) in human cancers with focus on breast cancer

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that <it>NDRG2 </it>mRNA is down-regulated or undetectable in various human cancers and cancer cell-lines. Although the function of <it>NDRG2 </it>is currently unknown, high <it>NDRG2 </it>expression correlates with improved prognosis in high-grade gliomas, gastric cancer and hepatocellular carcinomas. Furthermore, <it>in vitro </it>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 <it>NDRG2 </it>mRNA in several human cancers, with focus on breast cancer, by examining affected and normal tissue.</p> <p>Methods</p> <p>By labelling a human Cancer Profiling Array with a radioactive probe against <it>NDRG2</it>, we evaluated the level of <it>NDRG2 </it>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 <it>NDRG2 </it>and <it>MYC </it>mRNA in thyroid gland cancer and breast cancer, using a distinct set of normal and tumor samples.</p> <p>Results</p> <p>From the Cancer Profiling Array, we saw that the level of <it>NDRG2 </it>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 <it>NDRG2 </it>mRNA expression in tumor tissue compared to normal tissue. Using quantitative RT-PCR, we observed a significant reduction in the level of <it>NDRG2 </it>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. <it>MYC </it>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 <it>MYC </it>and <it>NDRG2 </it>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 <it>MYC </it>and <it>NDRG2 </it>mRNA are regulated together.</p> <p>Conclusion</p> <p>Expression of <it>NDRG2 </it>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 <it>NDRG2 </it>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 <it>NDRG2 </it>mRNA in tumor tissue compared to normal tissue.</p

Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>It has recently been shown that <it>NDRG2 </it>mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high <it>NDRG2 </it>expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine <it>NDRG2 </it>mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages <it>NDRG2 </it>down-regulation occurs during colonic carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>NDRG2 </it>in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). <it>NDRG2 </it>levels were normalised to <it>β-actin</it>.</p> <p>Results</p> <p><it>NDRG2 </it>mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, <it>NDRG2 </it>expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for <it>NDRG2 </it>levels to decrease with increasing Dukes' stage (p < 0.05).</p> <p>Conclusion</p> <p>Our results demonstrate that expression of <it>NDRG2 </it>is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether <it>NDRG2 </it>down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma.</p

Expression of is down-regulated in high-risk adenomas and colorectal carcinoma-0

<p><b>Copyright information:</b></p><p>Taken from "Expression of is down-regulated in high-risk adenomas and colorectal carcinoma"</p><p>http://www.biomedcentral.com/1471-2407/7/192</p><p>BMC Cancer 2007;7():192-192.</p><p>Published online 12 Oct 2007</p><p>PMCID:PMC2099434.</p><p></p>individuals (Control), normal and affected tissue from the same individual with adenomas (low- or high-risk) and colorectal carcinoma. Normal (adjacent): normal sample close to the carcinoma, Normal (distant): normal sample far from the carcinoma. Each dot represents mean values of triplicate determinations. *** p < 0.001 compared to the control group using one-way ANOVA with a Tukey's post test. A trend of decreased expression with increasing tumor grade was observed in affected tissue (p < 0.001)

Expression of is down-regulated in high-risk adenomas and colorectal carcinoma-1

<p><b>Copyright information:</b></p><p>Taken from "Expression of is down-regulated in high-risk adenomas and colorectal carcinoma"</p><p>http://www.biomedcentral.com/1471-2407/7/192</p><p>BMC Cancer 2007;7():192-192.</p><p>Published online 12 Oct 2007</p><p>PMCID:PMC2099434.</p><p></p>h 13 samples categorised as Dukes' A, 19 samples as Dukes' B and 18 samples as Dukes' C. The graph shows the normalised level of mRNA in samples from the different Dukes' stages. Calculating linear regression using each column of data resulted in a statistically significant linear trend (p < 0.05) for a decrease in level with increasing Dukes' stage

Expression of is down-regulated in high-risk adenomas and colorectal carcinoma-3

<p><b>Copyright information:</b></p><p>Taken from "Expression of is down-regulated in high-risk adenomas and colorectal carcinoma"</p><p>http://www.biomedcentral.com/1471-2407/7/192</p><p>BMC Cancer 2007;7():192-192.</p><p>Published online 12 Oct 2007</p><p>PMCID:PMC2099434.</p><p></p>individuals (Control), normal and affected tissue from the same individual with adenomas (low- or high-risk) and colorectal carcinoma. Normal (adjacent): normal sample close to the carcinoma, Normal (distant): normal sample far from the carcinoma. Each dot represents mean values of triplicate determinations. *** p < 0.001 compared to the control group using one-way ANOVA with a Tukey's post test. A trend of decreased expression with increasing tumor grade was observed in affected tissue (p < 0.001)