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Published in: Tumor Biology 6/2012

01-12-2012 | Research Article

RHBDD2: a 5-fluorouracil responsive gene overexpressed in the advanced stages of colorectal cancer

Authors: Ezequiel Lacunza, R. Canzoneri, M. E. Rabassa, A. Zwenger, A. Segal-Eiras, M. V. Croce, M. C. Abba

Published in: Tumor Biology | Issue 6/2012

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Abstract

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.
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Literature
2.
3.
go back to reference Urban S, Lee JR, Freeman M. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell. 2001;107(2):173–82.PubMedCrossRef Urban S, Lee JR, Freeman M. Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell. 2001;107(2):173–82.PubMedCrossRef
4.
go back to reference Lee JR, Urban S, Garvey CF, Freeman M. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell. 2001;107(2):161–71.PubMedCrossRef Lee JR, Urban S, Garvey CF, Freeman M. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell. 2001;107(2):161–71.PubMedCrossRef
5.
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277(2):301–8.PubMedCrossRef Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277(2):301–8.PubMedCrossRef
8.
go back to reference Krasinskas AM. EGFR signaling in colorectal carcinoma. Patholog Res Int. 2011;2011:932932.PubMed Krasinskas AM. EGFR signaling in colorectal carcinoma. Patholog Res Int. 2011;2011:932932.PubMed
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference Adrain C, Strisovsky K, Zettl M, et al. Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO Rep. 2011;12(5):421–7.PubMedCrossRef Adrain C, Strisovsky K, Zettl M, et al. Mammalian EGF receptor activation by the rhomboid protease RHBDL2. EMBO Rep. 2011;12(5):421–7.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference The Translational Genomics Research Institute. “Expression Project For Oncology (expO) Collects 1,000th Malignant Tumor Specimen.” ScienceDaily, 25 Oct. 2005. Web. 3 Sep. 2012. The Translational Genomics Research Institute. “Expression Project For Oncology (expO) Collects 1,000th Malignant Tumor Specimen.” ScienceDaily, 25 Oct. 2005. Web. 3 Sep. 2012.
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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.PubMed 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.PubMed
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
RHBDD2: a 5-fluorouracil responsive gene overexpressed in the advanced stages of colorectal cancer
Authors
Ezequiel Lacunza
R. Canzoneri
M. E. Rabassa
A. Zwenger
A. Segal-Eiras
M. V. Croce
M. C. Abba
Publication date
01-12-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0503-3

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