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Science 12 May 1989:
Vol. 244. no. 4905, pp. 707 - 712
DOI: 10.1126/science.2470152
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Articles

Science, Vol 244, Issue 4905, 707-712
Copyright © 1989 by American Association for the Advancement of Science

articles

Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer

DJ Slamon, W Godolphin, LA Jones, JA Holt, SG Wong, DE Keith, WJ Levin, SG Stuart, J Udove, A Ullrich, and al. et

Department of Medicine, U.C.L.A. School of Medicine 90024.

Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.


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B. Xiang, K. Chatti, H. Qiu, B. Lakshmi, A. Krasnitz, J. Hicks, M. Yu, W. T. Miller, and S. K. Muthuswamy (2008)
PNAS 105, 12463-12468
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Chromosomal Abnormalities in Cancer.
S. Frohling and H. Dohner (2008)
N. Engl. J. Med. 359, 722-734
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Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells.
M. Lombardi, G. Castoria, A. Migliaccio, M. V. Barone, R. Di Stasio, A. Ciociola, D. Bottero, H. Yamaguchi, E. Appella, and F. Auricchio (2008)
J. Cell Biol. 182, 327-340
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Results of the First Phase I Clinical Trial of the Novel Ii-Key Hybrid Preventive HER-2/neu Peptide (AE37) Vaccine.
J. P. Holmes, L. C. Benavides, J. D. Gates, M. G. Carmichael, M. T. Hueman, E. A. Mittendorf, J. L. Murray, A. Amin, D. Craig, E. von Hofe, et al. (2008)
J. Clin. Oncol. 26, 3426-3433
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Identification of a Novel Immunogenic HLA-A*0201-Binding Epitope of HER-2/neu with Potent Antitumor Properties.
A. D. Gritzapis, I. F. Voutsas, E. Lekka, N. Tsavaris, I. Missitzis, P. Sotiropoulou, S. Perez, M. Papamichail, and C. N. Baxevanis (2008)
J. Immunol. 181, 146-154
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Activity of lapatinib is independent of EGFR expression level in HER2-overexpressing breast cancer cells.
D. Zhang, A. Pal, W. G. Bornmann, F. Yamasaki, F. J. Esteva, G. N. Hortobagyi, C. Bartholomeusz, and N. T. Ueno (2008)
Mol. Cancer Ther. 7, 1846-1850
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Single-chain antibody/activated BID chimeric protein effectively suppresses HER2-positive tumor growth.
X.-C. Qiu, Y.-M. Xu, F. Wang, Q.-Y. Fan, L.-F. Wang, B.-A. Ma, L.-T. Jia, J. Zhao, Y.-L. Meng, L.-B. Yao, et al. (2008)
Mol. Cancer Ther. 7, 1890-1899
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Efficacy and Safety of Lapatinib As First-Line Therapy for ErbB2-Amplified Locally Advanced or Metastatic Breast Cancer.
H. L. Gomez, D. C. Doval, M. A. Chavez, P. C.-S. Ang, Z. Aziz, S. Nag, C. Ng, S. X. Franco, L. W.C. Chow, M. C. Arbushites, et al. (2008)
J. Clin. Oncol. 26, 2999-3005
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Trastuzumab in the Adjuvant Treatment of Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
I. J. Dahabreh, H. Linardou, F. Siannis, G. Fountzilas, and S. Murray (2008)
Oncologist 13, 620-630
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Overcoming retinoic acid-resistance of mammary carcinomas by diverting retinoic acid from PPAR{beta}/{delta} to RAR.
T. T. Schug, D. C. Berry, I. A. Toshkov, L. Cheng, A. Y. Nikitin, and N. Noy (2008)
PNAS 105, 7546-7551
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Signaling through ShcA Is Required for Transforming Growth Factor {beta}- and Neu/ErbB-2-Induced Breast Cancer Cell Motility and Invasion.
J. J. Northey, J. Chmielecki, E. Ngan, C. Russo, M. G. Annis, W. J. Muller, and P. M. Siegel (2008)
Mol. Cell. Biol. 28, 3162-3176
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The Fibroblast Growth Factor-Inducible 14 Receptor Is Highly Expressed in HER2-Positive Breast Tumors and Regulates Breast Cancer Cell Invasive Capacity.
A. L. Willis, N. L. Tran, J. M. Chatigny, N. Charlton, H. Vu, S. A.N. Brown, M. A. Black, W. S. McDonough, S. P. Fortin, J. R. Niska, et al. (2008)
Mol. Cancer Res. 6, 725-734
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t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in Her2/ErbB2 mice through activation of both proliferative and survival pathways.
X. Meng, S. F. Shoemaker, S. O. McGee, and M. M. Ip (2008)
Carcinogenesis 29, 1013-1021
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Coordinated Epidermal Growth Factor Receptor Pathway Gene Overexpression Predicts Epidermal Growth Factor Receptor Inhibitor Sensitivity in Pancreatic Cancer.
A. Jimeno, A. C. Tan, J. Coffa, N.V. Rajeshkumar, P. Kulesza, B. Rubio-Viqueira, J. Wheelhouse, B. Diosdado, W. A. Messersmith, C. Iacobuzio-Donahue, et al. (2008)
Cancer Res. 68, 2841-2849
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Phosphatase and Tensin Homologue Deleted on Chromosome 10 Deficiency Accelerates Tumor Induction in a Mouse Model of ErbB-2 Mammary Tumorigenesis.
N. Dourdin, B. Schade, R. Lesurf, M. Hallett, R. J. Munn, R. D. Cardiff, and W. J. Muller (2008)
Cancer Res. 68, 2122-2131
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Crosstalk between the Estrogen Receptor and the HER Tyrosine Kinase Receptor Family: Molecular Mechanism and Clinical Implications for Endocrine Therapy Resistance.
G. Arpino, L. Wiechmann, C. K. Osborne, and R. Schiff (2008)
Endocr. Rev. 29, 217-233
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Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells.
K.-K. Kim, J. J. Lee, Y. Yang, K.-H. You, and J.-H. Lee (2008)
Carcinogenesis 29, 704-712
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Effects of gefitinib (Iressa) on mammary cancers: preventive studies with varied dosages, combinations with vorozole or targretin, and biomarker changes.
R. A. Lubet, E. Szabo, K. Christov, A. M. Bode, M. E. Ericson, V. E. Steele, M. M. Juliana, and C. J. Grubbs (2008)
Mol. Cancer Ther. 7, 972-979
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