Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 6/2001

01-12-2001 | Review

Update on HER-2 as a target for cancer therapy: The ERBB2 promoter and its exploitation for cancer treatment

Author: Helen C Hurst

Published in: Breast Cancer Research | Issue 6/2001

Login to get access

Abstract

Overexpression of the ERBB2 proto-oncogene is associated with amplification of the gene in breast cancer but increased activity of the promoter also plays a significant role. Members of two transcription factor families (AP-2 and Ets) show increased binding to the promoter in over-expressing cells. Consequently, strategies have been devised to target promoter activity, either through the DNA binding sites for these factors, or through another promoter sequence, a polypurine-polypyrimidine repeat structure. The promoter has also been exploited for its tumour-specific activity to direct the accumulation of cytotoxic compounds selectively within cancer cells. Our current understanding of the ERBB2 promoter is reviewed and the status of these therapeutic avenues is discussed.
Literature
1.
Yu DH, Hung MC: Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene. 2000, 19: 6115-6121. 10.1038/sj.onc.1203972.CrossRefPubMed
2.
Kraus M, Popescu N, Amsbaugh S, King C: Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 1987, 6: 605-610.PubMedPubMedCentral
3.
Bates NP, Hurst HC: Transcriptional regulation of type I receptor tyrosine kinases in the mammary gland. J Mammary Gland Biol Neoplasia. 1997, 2: 153-163. 10.1023/A:1026303814855.CrossRefPubMed
4.
Scott GK, Chang CH, Erny KM, Xu F, Fredericks WJ, Rauscher FJ, Thor AD, Benz CC: Ets regulation of the erbB2 promoter. Oncogene. 2000, 19: 6490-6502. 10.1038/sj.onc.1204041.CrossRefPubMed
5.
Ishii S, Imamoto F, Yamanishi Y, Toyoshima K, Yamamoto T: Characterisation of the promoter region of the human c-erbB-2 protooncogene. Proc Natl Acad Sci USA. 1987, 84: 4374-4378.CrossRefPubMedPubMedCentral
6.
Tal M, King C, Kraus M, Ullrich A, Schlessinger J, Givol D: Human her2 (neu) promoter: evidence for multiple mechanisms for transcriptional initiation. Mol Cell Biol. 1987, 7: 2597-2601.CrossRefPubMedPubMedCentral
7.
Scott G, Daniel J, Xiong X, Maki R, Kabat D, Benz C: Binding of an ETS-related Protein within the DNase I hypersensitive site of the HER2/neu promoter in human breast cancer cells. J Biol Chem. 1994, 269: 19848-19858.PubMed
8.
Bates NP, Hurst HC: An intron 1 enhancer element mediates oestrogen-induced suppression of ERBB2 expression. Oncogene. 1997, 15: 473-481. 10.1038/sj.onc.1201368.CrossRefPubMed
9.
Nezu M, Sasaki H, Kuwahara Y, Ochiya T, Yamada Y, Sakamoto H, Tashiro H, Yamazaki M, Ikeuchi T, Saito Y, Terada M: Identification of a novel promoter and exons of the c-ERBB-2 gene. Biochem Biophys Res Commun. 1999, 258: 499-505. 10.1006/bbrc.1999.0634.CrossRefPubMed
10.
Hollywood DP, Hurst HC: A novel transcription factor, OB2-1, is required for overexpression of the proto-oncogene c-erbB-2 in mammary tumour lines. EMBO J. 1993, 12: 2369-2375.PubMedPubMedCentral
11.
Bosher JM, Williams T, Hurst HC: The developmentally regulated transcription factor AP-2 is involved in c-erbB-2 overexpression in human mammary carcinoma. Proc Natl Acad Sci USA. 1995, 92: 744-747.CrossRefPubMedPubMedCentral
12.
Bosher JM, Totty NF, Hsuan JJ, Williams T, Hurst HC: A family of AP-2 proteins regulates c-erbB-2 expression in mammary carcinoma. Oncogene. 1996, 13: 1701-1707.PubMed
13.
Turner BC, Zhang J, Gumbs AA, Maher MG, Kaplan L, Carter D, Glazer PM, Hurst HC, Haffty BC, Williams T: Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Cancer Res. 1998, 58: 5466-5472.PubMed
14.
Xing XM, Wang SC, Xia WY, Zou YY, Shao RP, Kwong KY, Yu ZM, Zhang S, Miller S, Huang L, Hung MC: The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis. Nat Med. 2000, 6: 189-195. 10.1038/72294.CrossRefPubMed
15.
Benz CC, O'Hagan RC, Richter B, Scott GK, Chang CH, Xiong XH, Chew K, Ljung BM, Edgerton S, Thor A, Hassell JA: Her2/neu and the ets transcription activator PEA3 are co-ordinately up-regulated in human breast-cancer. Oncogene. 1997, 15: 1513-1525. 10.1038/sj.onc.1201331.CrossRefPubMed
16.
Hollywood DP, Hurst HC: Targeting gene transcription: a new strategy to downregulate c-erbB-2 expression in mammary carcinoma. Br J Cancer. 1995, 71: 753-757.CrossRefPubMedPubMedCentral
17.
Chiang SY, Burli RW, Benz CC, Gawron L, Scott GK, Dervan PB, Beerman TA: Targeting the Ets binding site of the HER2/neu promoter with pyrrole-imidazole polyamides. J Biol Chem. 2000, 275: 24246-24254. 10.1074/jbc.M000820200.CrossRefPubMed
18.
Okada T, Amanuma H, Okada Y, Obata M, Hayashi Y, Yamaguchi K, Yamashita J: Inhibition of gene-expression from the human c-erbB gene promoter by a retroviral vector expressing antigene RNA. Biochem Biophys Res Commun. 1997, 240: 203-207. 10.1006/bbrc.1997.7563.CrossRefPubMed
19.
Beerli RR, Segal DJ, Dreier B, Barbas CF: Toward controlling gene-expression at will: specific regulation of the erbb-2/her-2 promoter by using polydactyl zinc-finger proteins constructed from modular building-blocks. Proc Natl Acad Sci USA. 1998, 95: 14628-14633. 10.1073/pnas.95.25.14628.CrossRefPubMedPubMedCentral
20.
Harris J, Gutierrez AA, Hurst HC, Sikora K, Lemoine NR: Gene therapy for cancer using tumour-specific prodrug activation. Gene Ther. 1994, 1: 170-175.PubMed
21.
Pandha HS, Martin LA, Rigg A, Hurst HC, Stamp GWH, Sikora K, Lemoine NR: Genetic prodrug activation therapy for breast cancer: a phase I clinical trial of ERBB2-directed suicide gene expression. J Clin Oncol. 1999, 17: 2180-2189.PubMed
22.
Vassaux G, Hurst HC, Lemoine NR: Insulation of a conditionally expressed transgene in an adenoviral vector. Gene Ther. 1999, 6: 1192-1197. 10.1038/sj.gt.3300910.CrossRefPubMed
23.
Ring CJA, Blouin P, Martin LA, Hurst HC, Lemoine NR: Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug-activiating enzyme. Gene Ther. 1997, 4: 1045-1052. 10.1038/sj.gt.3300510.CrossRefPubMed
24.
Stackhouse MA, Buchsbaum DJ, Kancharla SR, Grizzle WE, Grimes C, Laffoon K, Pederson LC, Curiel DT: Specific membrane receptor gene expression targeted with radiolabeled peptide employing the erbB-2 and DF3 promoter elements in adenoviral vectors. Cancer Gene Ther. 1999, 6: 209-219. 10.1038/sj.cgt.7700049.CrossRefPubMed
25.
Balda MS, Matter K: The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J. 2000, 19: 2024-2033. 10.1093/emboj/19.9.2024.CrossRefPubMedPubMedCentral
Metadata
Title
Update on HER-2 as a target for cancer therapy: The ERBB2 promoter and its exploitation for cancer treatment
Author
Helen C Hurst
Publication date
01-12-2001
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2001
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr329

Other articles of this Issue 6/2001

Breast Cancer Research 6/2001 Go to the issue

Commentary

Wnt signaling in breast cancer: have we come full circle?

Review

Update on HER-2 as a target for cancer therapy: Alternative strategies for targeting the epidermal growth factor system in cancer

Review

Tumour-stromal interactions Reciprocal regulation of extracellular matrix proteins and ovarian steroid activity in the mammary gland

Review

Update on HER-2 as a target for cancer therapy: HER2/neu peptides as tumour vaccines for T cell recognition

Review

Update on HER-2 as a target for cancer therapy: Herceptin in the clinical setting

Review

Intracellular signaling pathways of ErbB2/HER-2 and family members
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits