Her-2 oncogene

Laakso M, Tanner M, Isola J. Dual-colour chromogenic in situ hybridization for testing of HER-2 oncogene amplification in archival breast tumours. J Pathol 2006 210(1) 3-9. 

Isola J, Tanner M, Forsyth A, Cooke TG, Watters AD, Bartlett JM. Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization. Clin Cancer Res 2004 10(14) 4793-8. 

Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer prognostic factor, predictive factor, and target for therapy. Oncologist 1998 3 237-252. 

Pietras RJ, Poen JC, Gallardo D, WongvipatPN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999 59(6) 1347-1355. 

Pietras RJ, Pegram MD, Finn RS, et al. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 1998 17 2235-2249. 

Zhang L, Hung MC. Sensitization of HER-2/neu-over-expressing non-small cell lung cancer cell to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Oncogene 1996 12 571-576. 

Pegram M, Hsu S, Lewis G, Pietras R. 1999. Inhibitory effects of combination of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancer. Oncogene. 18 2241-2251. 

HER-2/nen gene was first discovered as a transforming oncogene in a series of ethyl nitrosourea-induced rat neuroblastomas, where it was called neu (Schecter et al., 1984). Approximately 15 years ago, this oncogene was isolated independently by two separate groups, which named it HER-2 (Coussens et al., 1985) and c-erbB-2 (Semba et al., 1985), respectively. Further evidence revealed that the two genes were the same (Schechter et al., 1985), and it was renamed HER-2Ineu. 

It is interesting to note that expression and secretion of an aberrant HER-2 splice variant has been reported in various cell lines and tissues, which can interfere with the oncogenic HER-2 activity (Aigner et al., 2001). Expression of this truncated 100-kDa HER-2 variant encodes the extracellular domain of HER-2 and inhibits growth factor-mediated tumor cell proliferation. The exact role played by this variant during the progression of human cancer is not clear. 

Wood et al. (1991) have used the Southern hybridization method for detecting DNA amplification and a possible structural rearrangement of the HER-2/nen oncogene in 1 of 12 bladder tumors. Amplification of this oncogene in the tumor was sixfold that of oncogene found in placental DNA. Approximately 36% of the tumors studied overexpressed HER-2 mRNA, which was 3- to 38-fold that of normal urothelium. HER-2 overexpression occurred in superficial and invasive tumors. Deoxyribonucleic acid amplification occurs infrequently in bladder carcinoma, in contrast to its occurrence in some other carcinomas. Immunohistochemical analysis has shown that pi85 HER-2 polyclonal antibody is specific for HER-2 protein overexpression in bladder carcinoma. This study was carried out prior to the use of Herceptin. 

Disis, M. L., Grabstein, K. H., Sleath, R. R., and Cheever, M. A. 1999. Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. Clin. Cancer Res. 5 1289-1297. 

Pietras, R. J., Fendly, B. M., Chazin, V. R., Pegram, M. D., Howell, S. B., and Slamon, D. J. 1994. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 9 1829-1838. 

Press, M. F., Hung, G., Godolphin, W., and Slamon, D. J. 1994. Sensitivity of HER-2/neu antibodies in archival tissue samples Potential source of error in immunohistochemical studies of oncogene expression. Cancer Res. 54 2771-2777. 

Ross, J. S., Sheehan, C. E., and Fletcher, J. A. 2001. HER-2/neu oncogene amplification determined by fluorescence in situ hybridization. In Molecular Pathology Protocols (A. A. Killeen, ed.), pp. 93-104. Humana Press, Totowa, NJ. 

Pegram, M., Hsu, S., Lewis, G., Pietras, R., Beryt, M., Sliwkowski, M., Coombs, D., Baly, D., Kabbinavar, F., and Slamon, D. (1999). Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 18, 2241-2251. 

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