Existing users Log In New users Sign up


EGFR & HER2 are frequently elevated in colon cancer

DISCOVERIES REPORTS (ISSN 2393249X), 2014, September-December issue

CITATION: 

SiShi L, Buchbinder E, Wu L, Bjorge JD, Fujita DJ, Zhu S. EGFR and HER2 levels are frequently elevated in colon cancer cells. Discoveries Reports 2014, Sep-Dec; 1(1): e1.  DOI: 10.15190/drep.2014.1

 Submitted: August 24th, 2013; Revised: February 2nd, 2014; Accepted: February 2nd, 2014Published: February 3rd, 2014;

 GO BACK to 2014, September-December issue

 GO BACK to DISCOVERIES REPORTS

EGFR and HER2 levels are frequently elevated in colon cancer cells

SiShi Li (1), Elizabeth Buchbinder (2), Lihua Wu (1), Jeffrey D. Bjorge (3), Donald J. Fujita (3), Shudong Zhu (1,*) 

(1) School of Life Sciences, State Key Laboratory of Medical Genetics, Central South University, Changsha, China;
(2) Department of of Hematology and Oncology, Beth Israel Deaconess Medical Center, MA, USA;
(3) Victor Babes National Institute of Pathology, Bucharest, Romania;
(4) Bruker Nano Surfaces Division, Karlsruhe, Germany;

*Correspondence toShudong Zhu, Ph.D, School of Life Sciences, Central South University,  172 TongZiPo Rd, Changsha, China. Phone: 731 8265 0460; E-mail: shudongzhu@csu.edu.cn

Abstract

OBJECTIVE: Correlation between EGFR/HER2 protein levels and colon cancer prognosis has been suggested. However, reports on the prevalence of EGFR/HER2 overexpression have been divergent and inconclusive due to technical variations. The uncertainty of the prevalence greatly affects decisions on therapeutic interventions targeting both molecules. We aim at evaluating the prevalence and significance of EGFR/HER2 overexpression in colon cancer cell lines.

METHODS: We employed normal colon epithelial cell strain FHC and examined EGFR and HER2 levels in a series of colon carcinoma cell lines using Western blotting, and evaluated the effectiveness of siRNA targeting expression of the genes to inhibit the oncogenic properties of colon cancer cells.

RESULTS: We found that (1) as compared with normal colon epithelial cells, EGFR levels and HER2 levels were significantly increased in 7 of the 8 colon cancer cell lines examined (2) siRNA targeting EGFR or HER2 reduced colony formation in soft agar of SW480 colon cancer cells, and combined treatment further reduced the colony formation ability. 

CONCLUSION: These results suggested that EGFR and/or HER2 elevation play an important role in the development of the majority of colon cancers, and targeting EGFR and/or HER2 could serve as an effective common strategy for therapeutic intervention or prevention of colon cancer.

 

Access full text of the manuscript here: 

References

1. Hynes NE, Macdonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009; 21: 177-184.

2. Han W, Lo HW. Landscape of EGFR signaling network network in human cancers: biology and therapeutic response in relation to receptor subcellular locations. Cancer Lett. 2012; 318: 124-134.

3. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-182.

4. Kapitanovic S, Radosevic S, Kapitanovic M, Andelinovic S, Ferencic Z, Tavassoli M et al. The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology 1997; 112: 1103-1113.

5. Hong L, Han Y, Zhang H, Zhao Q, Yang J, Ahuja N. High expression of epidermal growth factor receptor might predict poor survival in patients with colon cancer: a meta-analysis. Genet Test Mol Biomarkers 2013; 17: 348-351.

6. Bolen JB, Veillette A, Schwartz AM, Deseau V, Rosen N. Activation of pp60c-src protein kinase activityin human colon carcinoma. Proc Natl Acad Sci U S A 1987; 84: 2251-2255.

7. Cartwright CA, Kamps MP, Meisler AI, Pipas JM, Eckhart W. pp60c-src activation in human colon carcinoma. J Clin Invest. 1989; 83: 2025-2033, 1989.

8. Talamonti MS, Roh MS, Curley SA, Gallick GE. Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer. J Clin Invest. 1993; 91: 53-60.

9. Irby R, Mao W, Coppola D, Jove R, Gamero A, Cuthbertson D, Fujita DJ, Yeatman TJ. Overexpression of normal c-Src in poorly metastatic human colon cancer cells enhances primary tumor growth but not metastatic potential. Cell Growth Differ. 1997; 8: 1287-1295.

10. Staley CA, Parikh NU, Gallick GE. Decreased tumorigenicity of a human colon adenocarcinoma cell line by an antisense expression vector specific for c-Src. Cell Growth Differ. 1997; 8: 269-274.

11. Zhu S, Bjorge JD, Cheng HC, Fujita DJ. Decreased CHK protein levels are associated with Src activation in colon cancer cells. Oncogene 2008; 27: 2027-2034.

12. Bjorge JD, Kudlow JE. Epidermal growth factor receptor synthesis is stimulated by phorbol ester and epidermal growth factor. Evidence for a common mechanism. J Biol Chem. 1987; 262: 6615-6622.

13. Koretz K, Schlag P, Moller P. Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma. Virchows Arch A Pathol Anat Histopathol. 1990; 416: 343-349.

14. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995; 19: 183-232.

15. Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001; 19: 554-568.

16. Schuell B, Gruenberger T, Scheithauer W, Zielinski C, Wrba F. HER 2/neu protein expression in colorectal cancer. BMC Cancer 2006; 6: 123.

17. Montesano R, Drevon C, Kuroki T, Saint VL, Handleman S, Sanford KK, DeFeo D, Weinstein IB. Test for malignant transformation of rat liver cells in culture: cytology, growth in soft agar, and production of plasminogen activator. J Natl Cancer Inst. 1977; 59: 1651-1658.

18. Osako T, Miyahara M, Uchino S, Inomata M, Kitano S, Kobayashi M. Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the correlation with patient survival. Oncology 1998; 55: 548-555.

19. Hu YP, Venkateswarlu S, Sergina N, Howell G, St Clair P, Humphrey LE, Li W et al. Reorganization of ErbB family and cell survival signaling after Knock-down of ErbB2 in colon cancer cells. J Biol Chem. 2005; 280: 27383-27392.

20. Learn PA, Krishnegowda N, Talamantez J, Kahlenberg MS. Compensatory increases in Her-2/neu activation in response to EGFR tyrosine kinase inhibition in colon cancer cell lines. J Surg Res. 2006; 136: 227-231.

21. Reid A, Vidal L, Shaw H, de Bono J. Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). Eur J Cancer 2007; 43: 481-489.

22. Alroy I. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 1997; 410(1): 83-6.

23. Yarden Y, Schlessinger J. Self-phosphorylation of epidermal growth factor receptor: evidence for a model of intermolecular allosteric activation. Biochemistry 1987; 26: 1434-1442.

24. Wheeler DL, Iida M, Kruser TJ, Nechrebecki MM, Dunn EF, Armstrong EA, Huang S, Harari PM. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol Ther. 2009; 8: 696-703.

25. Andersen P, Villingshoj M, Poulsen HS, Stockhausen MT. Improved response by co-targeting EGFR/ EGFRvIII and Src family kinases in human cancer cells. Cancer Invest. 2009; 27: 178-183.

26. Chong CR, Jänne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med. 2013; 19: 1389-1400. 

News & Events Latest news from Discoveries Reports

  • 2015 | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! First citations to articles published in Discoveries Reports are included! Search for the article's title (recommended) or the authors:

    Google Scholar Search
  • 2014 | Discoveries Reports

    DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries Reports. DOI uniquely identifies an article and is provided by CrossRef.

    CrossRef
  • 2014 | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)
    There are NO fees for the manucript submission or publishing of the accepted manuscripts.

    read more
  • 2014 | DISCOVERIES REPORTS

    We are now ACCEPTING MANUSCRIPTS for DISCOVERIES REPORTS, publishing inovative and important research findings from all areas related to Medicine, Biology and Chemistry. We are also accepting experimental articles that validate/invalidate highly used reagents in current publications (ex. antibodies) and selected articles presenting negative data with impact and of wide scientific interest ...

    read more
Member Login
Free Registration Click here to sign up
Copyright © 2013 Applied Systems. All Rights Reserved.