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Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Short communication

Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes identical to those induced by canonical MMTV

Authors: Robert D Bruno, Sonia M Rosenfield, Gilbert H Smith

Published in: Molecular Cancer | Issue 1/2013

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Abstract

Background

The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings

We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.

Conclusions

These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.
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Literature
1.
go back to reference Nandi S, McGrath M: Mammary neoplasia in mice. Adv Cancer Res. 1973, 17: 353-414.CrossRef Nandi S, McGrath M: Mammary neoplasia in mice. Adv Cancer Res. 1973, 17: 353-414.CrossRef
2.
go back to reference Moore D, Long C, Vaidya A, Sheffield J, Dion A, Lasfargues E: Mammary tumor viruses. Adv Cancer Res. 1979, 29: 347-418.CrossRefPubMed Moore D, Long C, Vaidya A, Sheffield J, Dion A, Lasfargues E: Mammary tumor viruses. Adv Cancer Res. 1979, 29: 347-418.CrossRefPubMed
3.
go back to reference Heston WE, Vlahakis G: Mammary tumors, plaques, and hyperplastic alveolar nodules in various combinations of mouse inbred strains and the different lines of the mammary tumor virus. Int J Cancer. 1971, 7: 141-148. 10.1002/ijc.2910070116CrossRefPubMed Heston WE, Vlahakis G: Mammary tumors, plaques, and hyperplastic alveolar nodules in various combinations of mouse inbred strains and the different lines of the mammary tumor virus. Int J Cancer. 1971, 7: 141-148. 10.1002/ijc.2910070116CrossRefPubMed
4.
go back to reference Moore DH, Holben JA, Charney J: Biologic characteristics of some mouse mammary tumor viruses. J Natl Cancer Inst. 1976, 57: 889-896.PubMed Moore DH, Holben JA, Charney J: Biologic characteristics of some mouse mammary tumor viruses. J Natl Cancer Inst. 1976, 57: 889-896.PubMed
5.
go back to reference van Nie R, Verstraeten AA: Studies of genetic transmission of mammary tumour virus by C3Hf mice. Int J Cancer. 1975, 16: 922-931. 10.1002/ijc.2910160606CrossRefPubMed van Nie R, Verstraeten AA: Studies of genetic transmission of mammary tumour virus by C3Hf mice. Int J Cancer. 1975, 16: 922-931. 10.1002/ijc.2910160606CrossRefPubMed
6.
go back to reference Young LJ, DeOme KB, Blair PB, Pitelka DR, Cardiff RD: Development and characterization of the BALB/cNIV mouse strain. Cancer Res. 1984, 44: 4333-4336.PubMed Young LJ, DeOme KB, Blair PB, Pitelka DR, Cardiff RD: Development and characterization of the BALB/cNIV mouse strain. Cancer Res. 1984, 44: 4333-4336.PubMed
7.
go back to reference Puma JP, Fanning TG, Young LJ, Cardiff RD: Identification of a unique mouse mammary tumor virus in the BALB/cNIV mouse strain. J Virol. 1982, 43: 158-165.PubMedCentralPubMed Puma JP, Fanning TG, Young LJ, Cardiff RD: Identification of a unique mouse mammary tumor virus in the BALB/cNIV mouse strain. J Virol. 1982, 43: 158-165.PubMedCentralPubMed
8.
go back to reference Callahan R, Smith GH: Common integration sites for MMTV in viral induced mouse mammary tumors. J Mammary Gland Biol Neoplasia. 2008, 13: 309-321. 10.1007/s10911-008-9092-6PubMedCentralCrossRefPubMed Callahan R, Smith GH: Common integration sites for MMTV in viral induced mouse mammary tumors. J Mammary Gland Biol Neoplasia. 2008, 13: 309-321. 10.1007/s10911-008-9092-6PubMedCentralCrossRefPubMed
9.
go back to reference Callahan R, Mudunur U, Bargo S, Raafat A, McCurdy D, Boulanger C, Lowther W, Stephens R, Luke BT, Stewart C: Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors. Oncotarget. 2012, 3: 1320-1334.PubMedCentralCrossRefPubMed Callahan R, Mudunur U, Bargo S, Raafat A, McCurdy D, Boulanger C, Lowther W, Stephens R, Luke BT, Stewart C: Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors. Oncotarget. 2012, 3: 1320-1334.PubMedCentralCrossRefPubMed
10.
go back to reference Theodorou V, Kimm MA, Boer M, Wessels L, Theelen W, Jonkers J, Hilkens J: MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nat Genet. 2007, 39: 759-769. 10.1038/ng2034CrossRefPubMed Theodorou V, Kimm MA, Boer M, Wessels L, Theelen W, Jonkers J, Hilkens J: MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nat Genet. 2007, 39: 759-769. 10.1038/ng2034CrossRefPubMed
11.
go back to reference Klijn C, Koudijs MJ, Kool J, Ten Hoeve J, Boer M, de Moes J, Akhtar W, van Miltenburg M, Vendel-Zwaagstra A, Reinders MJ: Analysis of tumor heterogeneity and cancer gene networks using deep sequencing of MMTV-induced mouse mammary tumors. PLoS One. 2013, 8: e62113- 10.1371/journal.pone.0062113PubMedCentralCrossRefPubMed Klijn C, Koudijs MJ, Kool J, Ten Hoeve J, Boer M, de Moes J, Akhtar W, van Miltenburg M, Vendel-Zwaagstra A, Reinders MJ: Analysis of tumor heterogeneity and cancer gene networks using deep sequencing of MMTV-induced mouse mammary tumors. PLoS One. 2013, 8: e62113- 10.1371/journal.pone.0062113PubMedCentralCrossRefPubMed
12.
go back to reference Boulanger CA, Smith GH: Reducing mammary cancer risk through premature stem cell senescence. Oncogene. 2001, 20: 2264-2272. 10.1038/sj.onc.1204312CrossRefPubMed Boulanger CA, Smith GH: Reducing mammary cancer risk through premature stem cell senescence. Oncogene. 2001, 20: 2264-2272. 10.1038/sj.onc.1204312CrossRefPubMed
13.
go back to reference Sinha YN, Salocks CB, Vanderlaan WP, Vlahakis G: Evidence for an influence of mammary tumour virus on prolactin secretion in the mouse. J Endocrinol. 1977, 74: 383-392. 10.1677/joe.0.0740383CrossRefPubMed Sinha YN, Salocks CB, Vanderlaan WP, Vlahakis G: Evidence for an influence of mammary tumour virus on prolactin secretion in the mouse. J Endocrinol. 1977, 74: 383-392. 10.1677/joe.0.0740383CrossRefPubMed
14.
go back to reference Ben-David M, Heston WE, Rodbard D: Mammary tumor virus potentiation of endogenous prolactin effect on mammary gland differentiation. J Natl Cancer Inst. 1969, 42: 207-218.PubMed Ben-David M, Heston WE, Rodbard D: Mammary tumor virus potentiation of endogenous prolactin effect on mammary gland differentiation. J Natl Cancer Inst. 1969, 42: 207-218.PubMed
15.
go back to reference Sinha YN, Selby FW, Vanderlaan WP: The natural history of prolactin and GH secretion in mice with high and low incidence of mammary tumors. Endocrinology. 1974, 94: 757-764. 10.1210/endo-94-3-757CrossRefPubMed Sinha YN, Selby FW, Vanderlaan WP: The natural history of prolactin and GH secretion in mice with high and low incidence of mammary tumors. Endocrinology. 1974, 94: 757-764. 10.1210/endo-94-3-757CrossRefPubMed
16.
go back to reference Ross SR, Schmidt JW, Katz E, Cappelli L, Hultine S, Gimotty P, Monroe JG: An immunoreceptor tyrosine activation motif in the mouse mammary tumor virus envelope protein plays a role in virus-induced mammary tumors. J Virol. 2006, 80: 9000-9008. 10.1128/JVI.00788-06PubMedCentralCrossRefPubMed Ross SR, Schmidt JW, Katz E, Cappelli L, Hultine S, Gimotty P, Monroe JG: An immunoreceptor tyrosine activation motif in the mouse mammary tumor virus envelope protein plays a role in virus-induced mammary tumors. J Virol. 2006, 80: 9000-9008. 10.1128/JVI.00788-06PubMedCentralCrossRefPubMed
17.
go back to reference Arthur LO, Lovinger GG, Schochetman G: Establishment of a C3Hf mammary tumor cell line expressing endogenous mouse mammary tumor virus: antigenic and genetic relationships of this virus with highly oncogenic mouse mammary tumor viruses. J Virol. 1979, 32: 852-859.PubMedCentralPubMed Arthur LO, Lovinger GG, Schochetman G: Establishment of a C3Hf mammary tumor cell line expressing endogenous mouse mammary tumor virus: antigenic and genetic relationships of this virus with highly oncogenic mouse mammary tumor viruses. J Virol. 1979, 32: 852-859.PubMedCentralPubMed
18.
go back to reference Massey RJ, Arthur LO, Nowinski RC, Schochetman G: Monoclonal antibodies identify individual determinants on mouse mammary tumor virus glycoprotein gp52 with group, class, or type specificity. J Virol. 1980, 34: 635-643.PubMedCentralPubMed Massey RJ, Arthur LO, Nowinski RC, Schochetman G: Monoclonal antibodies identify individual determinants on mouse mammary tumor virus glycoprotein gp52 with group, class, or type specificity. J Virol. 1980, 34: 635-643.PubMedCentralPubMed
Metadata
Title
Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes identical to those induced by canonical MMTV
Authors
Robert D Bruno
Sonia M Rosenfield
Gilbert H Smith
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-79

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