+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A mouse mammary tumor virus-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-alpha



A mouse mammary tumor virus-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-alpha



Cancer Research 59(8): 1869-1876



Estrogens have important functions in mammary gland development and carcinogenesis. To better define these roles, we have used two previously characterized lines of genetically altered mice: estrogen receptor-alpha (ER alpha) knockout (ERKO) mice, which lack the gene encoding ER alpha, and mouse mammary virus tumor (MMTV)-Wnt-1 transgenic mice (Wnt-1 TG), which develop mammary hyperplasia and neoplasia due to ectopic production of the Wnt-1 secretory glycoprotein. We have crossed these lines to ascertain the effects of ER alpha deficiency on mammary gland development and carcinogenesis in mice expressing the Wnt-1 transgene. Introduction of the Wnt-1 transgene into the ERKO background stimulates proliferation of alveolar-like epithelium, indicating that Wnt-1 protein can promote mitogenesis in the absence of an ER alpha-mediated response. The hyperplastic glandular tissue remains confined to the nipple region, implying that the requirement for ER alpha in ductal expansion is not overcome by ectopic Wnt-1. Tumors were detected in virgin ERKO females expressing the Wnt-1 transgene at an average age (48 weeks) that is twice that seen in virgin Wnt-1 TG mice (24 weeks) competent to produce ER alpha. Prepubertal ovariectomy of Wnt-1 TG mice also extended tumor latency to 42 weeks. However, pregnancy did not appear to accelerate the appearance of tumors in Wnt-1 TG mice, and tumor growth rates were not measurably affected by late ovariectomy. Small hyperplastic mammary glands were observed in Wnt-1 TG males, regardless of ER alpha gene status; the glands were similar in appearance to those found in ERKO/Wnt-1 TG females. Mammary tumors also occurred in Wnt-1 TG males; latency tended to be longer in the heterozygous ER alpha and ERKO males (86 to 100 weeks) than in wild-type ER alpha mice (ca. 75 weeks). We conclude that ectopic expression of the Wnt-1 proto-oncogene can induce mammary hyperplasia and tumorigenesis in the absence of ER alpha in female and male mice. The delayed time of tumor appearance may depend on the number of cells at risk of secondary events in the hyperplastic glands, on the carcinogenesis-promoting effects of ER alpha signaling, or on both.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 010070729

Download citation: RISBibTeXText

PMID: 10213494


Related references

Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations. American Journal of Pathology 140(5): 1131-1146, 1992

Mammary tumorigenesis in feral mice: identification of a new int locus in mouse mammary tumor virus (Czech II)-induced mammary tumors. Journal of Virology 61(1): 66-74, 1987

Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53172H transgene: Influence of FVB background on tumor latency and identification of novel sites of proviral insertion. American Journal of Pathology 161(6): 2241-2253, 2002

Studies on the mouse mammary tumor agent mta part 2 cytochemistry of amino peptidase in normal mammary gland of c 57 bl spontaneous and virus induced mammary tumors in r 111 and c 57 bl mouse strains respectively and in cell lines producing the mammary tumor virus. Acta Histochemica: 181-188, 1970

Urethane induced mammary tumorigenesis in a murine mammary tumor virus murine mammary tumor virus positive mouse strain evidence for a keratinized nodule as a murine mammary tumor virus negative precursor lesion for squamous cell tumors. Journal of the National Cancer Institute 73(4): 935-942, 1984

Massive mammary gland infection and pregnancy-dependent mammary tumor development in mice infected neonatally with mouse mammary tumor virus (SW) but not in mice infected as adults, despite a dramatic local response. European Journal of Immunology 27(9): 2145-2151, 1997

Mouse mammary tumor virus dna organization during mammary tumorigenesis in balb c mice. Abstracts of the Annual Meeting of the American Society for Microbiology 80: ABSTRACT 666, 1980

Mouse mammary tumor virus and mammary tumorigenesis in wild mice. Pathology International. 46(12): 919-932, 1996

Mammary tumors in feral mice lacking mouse mammary tumor virus dna. Journal of Experimental Pathology (New York) 2(2): 93-98, 1985

Alterations of acquired mouse mammary tumor virus DNA during mammary tumorigenesis in BALB/cfC3H mice. Journal of the National Cancer Institute 71(5): 1011-1019, 1983

Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice. Journal of Steroid Biochemistry and Molecular Biology 95(1-5): 9-15, 2005

BALB/Mtv-null mice responding to strong mouse mammary tumor virus superantigens restrict mammary tumorigenesis. Journal of Virology 83(1): 484-488, 2008

Immune response to mouse mammary tumor virus in mice lacking the alpha/beta interferon or the gamma interferon receptor. Journal of Virology 72(4): 2638-2646, 1998

Mammary gland development in transgenic mice expressing a dominant-negative transforming growth factor-beta type II receptor under the control of the mouse mammary tumor virus promoter/enhancer. Proceedings of the American Association for Cancer Research Annual Meeting 36(0): 188, 1995

Estrogen Binding in Mammary Tissue of C3H Mice With or Without the Mouse Mammary Tumor Virus. Oncology 35(3): 127-131, 1978