In previous studies, we identified rhomboid domain containing 2 (RHBDD2) gene to be markedly overexpressed in breast cancer patients that developed recurrence of the disease. In this study, we evaluated for the first time RHBDD2 gene expression in colorectal cancer (CRC). Five public available DNA microarray studies were compiled in a homogeneous dataset of 906 colorectal samples. The statistical analysis of these data showed a significant increase of RHBDD2 expression in the advanced stages of CRC (p < 0.01). We validated these findings by immunohistochemistry on 130 colorectal tissue samples; RHBDD2 protein overexpression was also observed in the advanced stages of the disease (p < 0.001). In addition, we investigated RHBDD2 expression in response to the chemotherapy agent 5-fluorouracile (5FU). We detected a significant increase of RHBDD2 mRNA and protein after 5FU treatment (20–40 μM; p < 0.001). Overall, these results showed that RHBDD2 overexpression might play a role in colorectal cancer progression.
Colorectal cancer RHBDD2 gene expression 5FU treatment
This is a preview of subscription content, log in to check access.
This work was supported by CONICET (PIP 2131) and FONCYT (PICT 0275) grants.
Spano JP, Milano G, Vignot S, Khayat D. Potential predictive markers of response to EGFR-targeted therapies in colorectal cancer. Crit Rev Oncol Hematol. 2008;66(1):21–30.PubMedCrossRefGoogle Scholar
Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277(2):301–8.PubMedCrossRefGoogle Scholar
Krasinskas AM. EGFR signaling in colorectal carcinoma. Patholog Res Int. 2011;2011:932932.PubMedGoogle Scholar
Wang Y, Guan X, Fok KL, et al. A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis. Cell Mol Life Sci. 2008;65(23):3822–9.PubMedCrossRefGoogle Scholar
Yan Z, Zou H, Tian F, et al. Human rhomboid family-1 gene silencing causes apoptosis or autophagy to epithelial cancer cells and inhibits xenograft tumor growth. Mol Cancer Ther. 2008;7(6):1355–64.PubMedCrossRefGoogle Scholar
Zou H, Thomas SM, Yan Z-W, et al. Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation of EGFR growth signals in head and neck squamous cancer cells. FASEB J. 2009;23(2):425–32.PubMedCrossRefGoogle Scholar
Adrain C, Strisovsky K, Zettl M, et al. Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO Rep. 2011;12(5):421–7.PubMedCrossRefGoogle Scholar
Abba MC, Sun H, Hawkins KA, et al. Breast cancer molecular signatures as determined by SAGE: correlation with lymph node status. Mol Cancer Res. 2007;5(9):881–90.PubMedCrossRefGoogle Scholar
Abba MC, Lacunza E, Nunez MI, et al. Rhomboid domain containing 2 (RHBDD2): a novel cancer-related gene over-expressed in breast cancer. Biochim Biophys Acta. 2009;1792(10):988–97.PubMedCrossRefGoogle Scholar
The Translational Genomics Research Institute. “Expression Project For Oncology (expO) Collects 1,000th Malignant Tumor Specimen.” ScienceDaily, 25 Oct. 2005. Web. 3 Sep. 2012.Google Scholar
Jorissen RN, Gibbs P, Christie M, et al. Metastasis-associated gene expression changes predict poor outcomes in patients with Dukes stage B and C colorectal cancer. Clin Cancer Res. 2009;15(24):7642–51.PubMedCrossRefGoogle Scholar
Smith JJ, Deane NG, Wu F, et al. Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer. Gastroenterology. 2010;138(3):958–68.PubMedCrossRefGoogle Scholar
Mariadason JM, Arango D, Shi Q, et al. Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin. Cancer Res. 2003;63(24):8791–812.PubMedGoogle Scholar
Boyer J, Allen WL, McLean EG, et al. Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006;66(5):2765–77.PubMedCrossRefGoogle Scholar