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Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea

  • Preclinical Study
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Abstract

Previous studies show inhibitory effects of green tea in chemically induced mammary tumors or human tumor explants, but not in spontaneous tumor models that are more representative of human breast cancer. The C3(1)/SV40 mouse model is particularly suited for breast cancer prevention studies because it produces spontaneous ductal adenocarcinomas and a predictable time course for mammary tumorigenesis through a multistage progression similar to that occurring in humans. We therefore used this model to test the chemoprotective effects of green tea. Administration of 0.5% Polyphenon E (Poly E) (a standardized preparation of green tea extract) in drinking water delayed tumor onset and suppressed tumor growth by 40%, compared to tap water-fed animals, with no adverse side effects. Histological analysis of mammary glands showed that green tea slowed the progression of ductal lesions to advanced mammary intraepithelial neoplasias and suppressed tumor invasiveness. Green tea inhibited the proliferation of ductal epithelial cells and tumors and, overall, disrupted post-pubertal ductal growth. Immunohistochemical analyses also demonstrated that green tea inhibited angiogenesis through a decrease in both ductal epithelial and stromal VEGF expression and a decrease in intratumoral microvascular density. Our data strongly support the potential use of green tea as a breast cancer chemopreventive agent.

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Abbreviations

EGCG:

(-)-Epigallocatechin-3-gallate

SV40 Tag:

Simian virus 40 T-antigen

MIN:

Mammary intraepithelial neoplasias

Poly E:

Polyphenon E

TDLU:

Terminal ductal lobular units

VEGF:

Vascular endothelial growth factor

CD31:

Also known as PECAM-1 (platelet endothelial cell adhesion molecule-1)

MVD:

Microvascular density

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Acknowledgements

This work was supported by the generous donation of Mr. and Mrs. Gordon I. Segal (H.L., P.S.M., G.L.G.), Susan G. Komen Breast Cancer Foundation Postdoctoral Fellowship PDF0503835 (H.L.), Ludwig Fund for Cancer Research (G.L.G.), and UCCRC Immunology Application core facility funded by CCSG grant 5 P30 CA014599–32. We thank Dr. Yukihiko Hara from Mitsui Norin Co. Ltd for the generous supply of Polyphenon E, Jeffrey E. Green and Suzanne D. Conzen for their expertise in the C3(1)/SV40 mice, Thomas Krausz and Maria Tretiakova for their guidance in mammary gland histopathology, and the technical support of the University of Chicago Pathology Research Cores personnel.

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  1. The Ben May Department for Cancer Research, The University of Chicago, GCIS W330, 929 East 57th Street, Chicago, IL, 60637, USA

    Hoyee Leong, Priya S. Mathur & Geoffrey L. Greene

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  1. Hoyee Leong
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  2. Priya S. Mathur
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Correspondence to Geoffrey L. Greene.

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Leong, H., Mathur, P.S. & Greene, G.L. Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea. Breast Cancer Res Treat 107, 359–369 (2008). https://doi.org/10.1007/s10549-007-9568-x

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  • DOI: https://doi.org/10.1007/s10549-007-9568-x

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