Collagen mRNA levels changes during colorectal cancer carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different α(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of <it>type IV collagen (α1/α4/α6) </it>and <it>type VII collagen (α1) </it>during colorectal cancer carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>α1(IV), α4(IV), α6(IV), and α1(VII) </it>in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to <it>β-actin</it>. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients.</p> <p>Results</p> <p>The <it>α1(IV) </it>and <it>α1(VII) </it>mRNA levels were statistically significantly higher in colorectal cancer tissue (p < 0.001) as compared to corresponding tissue from healthy controls. This is an early event as tissue from adenomas also displayed a higher level. There were small changes in the levels of <it>α4(IV)</it>. The level of <it>α6(IV) </it>was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p < 0.01). The localisation of type IV and type VII collagen was visualized by immunohistochemical staining.</p> <p>Conclusion</p> <p>Our results suggest that the down-regulation of <it>α6(IV</it>) mRNA coincides with the acquisition of invasive growth properties, whereas <it>α1(IV) </it>and <it>α1(VII) </it>mRNAs were up-regulated already in dysplastic tissue. There are no differences in collagen expression between tissues from healthy individuals and normal tissues from affected individuals.</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