Trisomy chromosome 5 is a recurrent cytogenetic lesion in mammary tumors from parous MMTV-erbB-2 transgenic mice

Kim,Young   Mi; Ma,Zhikun; Lee,Seungjik; Lee, Jiyun; Li,Shibo; Yang,Xiaohe

doi:10.3892/ol.2011.373

November-December 2011 Volume 2 Issue 6

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November-December 2011 Volume 2 Issue 6

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Article

Trisomy chromosome 5 is a recurrent cytogenetic lesion in mammary tumors from parous MMTV-erbB-2 transgenic mice

Authors:
- Young Mi Kim
- Zhikun Ma
- Seungjik Lee
- Jiyun Lee
- Shibo Li
- Xiaohe Yang
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Affiliations: Department of Pediatrics, University of Oklahoma Health Sciences Center, OK 73104, USA, Human Nutrition Program, North Carolina Research Campus, Julius L. Chambers Biomedical/ Biotechnology Research Institute, North Carolina Central University, Kannapolis, NC 28081, USA
Pages: 1077-1081
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Published online on: August 4, 2011

https://doi.org/10.3892/ol.2011.373
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Abstract

erbB-2 is amplified or overexpressed in approximately 30% of human breast cancers, and has been associated with poor prognosis and therapeutic resistance. Previous studies have suggested that erbB-2 overexpression in transgenic mice induces genomic instability; however, the patterns of genetic lesions vary with individual model systems. The development of mammary tumors in multiparous murine mammary tumor virus (MMTV)-erbB-2 transgenic mice is accelerated due to hormonal interactions which induce the overexpression of MMTV‑mediated erbB-2. However, whether or not accelerated tumor development is associated with modified cytogenetic patterns remains to be determined. In this study, chromosomal changes were characterized in mammary tumor cells derived from multiparous MMTV-erbB-2 transgenic mice, and compared with tumor cells derived from control virgin mice. Immunohistochemistry and Western blotting were used to detect erbB-2 overexpression in mammary tissues. Each of the five tumors from the multiparous MMTV-erbB-2 transgenic mice was found to exhibit a marked chromosomal imbalance, compared with only one tumor with aberrant chromosomes among the five tumors from the control virgin mice. In particular, trisomy 5 and loss of the X chromosome were recurrent cytogenetic lesions in tumors from the parous mice, which is a novel pattern compared with previous studies. The elevated number of genetic lesions in tumors from parous mice, which were characterized by enhanced erbB-2 overexpression and increased receptor tyrosine kinase activation in the mammary glands, suggest a causal role for erbB-2 in the genomic instability present in these tumors. These data advance our understanding of erbB-2-mediated pathogenesis and underscore the role of cytogenetic alteration in this process.

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1	Bargmann CI, Hung MC and Weinberg RA: The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 319:226–230. 1986. View Article : Google Scholar : PubMed/NCBI
2	Schechter AL, Stern DF, Vaidyanathan L, et al: The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 312:513–516. 1984. View Article : Google Scholar : PubMed/NCBI
3	Koeplinger KA, Mildner AM, Leone JW, et al: Caspase 8: an efficient method for large-scale autoactivation of recombinant procaspase 8 by matrix adsorption and characterization of the active enzyme. Protein Expr Purif. 18:378–387. 2000. View Article : Google Scholar : PubMed/NCBI
4	Slamon DJ, Clark GM, Wong SG, et al: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 235:177–182. 1987. View Article : Google Scholar : PubMed/NCBI
5	Stern DF: Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Res. 2:176–183. 2000. View Article : Google Scholar : PubMed/NCBI
6	Prenzel N, Fischer OM, Streit S, et al: The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr Relat Cancer. 8:11–31. 2001. View Article : Google Scholar : PubMed/NCBI
7	Muthuswamy SK, Gilman M and Brugge JS: Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. Mol Cell Biol. 19:6845–6857. 1999.PubMed/NCBI
8	Siegel PM, Ryan ED, Cardiff RD, et al: Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. Embo J. 18:2149–2164. 1999. View Article : Google Scholar : PubMed/NCBI
9	Montagna C, Andrechek ER, Padilla-Nash H, et al: Centrosome abnormalities, recurring deletions of chromosome 4, and genomic amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by mutant HER2/neu. Oncogene. 21:890–898. 2002. View Article : Google Scholar
10	Jeruss JS, Liu NX, Chung Y, et al: Characterization and chromosomal instability of novel derived cell lines from a wt-erbB-2 transgenic mouse model. Carcinogenesis. 24:659–664. 2003. View Article : Google Scholar : PubMed/NCBI
11	Wagner KU, McAllister K, Ward T, et al: Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice. Transgenic Res. 10:545–553. 2001. View Article : Google Scholar : PubMed/NCBI
12	Anisimov VN, Popovich IG, Alimova IN, et al: Number of pregnancies and ovariectomy modify mammary carcinoma development in transgenic HER-2/neu female mice. Cancer Lett. 193:49–55. 2003. View Article : Google Scholar : PubMed/NCBI
13	Kim A, Liu B, Ordonez-Ercan D, et al: Functional interaction between mouse erbB3 and wild-type rat c-neu in transgenic mouse mammary tumor cells. Breast Cancer Res. 7:R708–R718. 2005. View Article : Google Scholar : PubMed/NCBI
14	Li B, Rosen JM, McMenamin-Balano J, et al: Neu/ERBB2 cooperates with p53-172H during mammary tumorigenesis in transgenic mice. Mol Cell Biol. 17:3155–3163. 1997.PubMed/NCBI
15	Brodie SG, Xu X, Li C, et al: Inactivation of p53 tumor suppressor gene acts synergistically with c-neu oncogene in salivary gland tumorigenesis. Oncogene. 20:1445–1454. 2001. View Article : Google Scholar : PubMed/NCBI
16	Hodgson JG, Malek T, Bornstein S, et al: Copy number aberrations in mouse breast tumors reveal loci and genes important in tumorigenic receptor tyrosine kinase signaling. Cancer Res. 65:9695–9704. 2005. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Trisomy chromosome 5 is a recurrent cytogenetic lesion in mammary tumors from parous MMTV-erbB-2 transgenic mice

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