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Loss of Stat5a delays mammary cancer progression in a mouse model

Oncogene volume 21, pages 4335–4339 (2002)Cite this article

Abstract

A genetic study was conducted to determine if activated Stat5a contributes to mammary carcinogenesis and to evaluate the mechanism. Similar to human breast cancers, a proportion of mammary adenocarcinomas in the WAP-TAg transgenic mouse model demonstrate constitutive Stat5a/b and Stat3 activation. Stat5a activation is linked to mammary epithelial cell survival and differentiation, and proliferation in hematopoetic cell lineages. Breeding WAP-TAg mice to mice carrying germ-line deletions of the Stat5a gene generated mice with reduced levels of Stat5a. Hemizygous loss of the Stat5a allele significantly reduced levels of Stat5a expression without altering mammary gland development or transgene expression levels. In comparison to mice carrying two wild-type Stat5a alleles, hemizygous loss of the Stat5a allele reduced the number of mice with palpable tumors at 7 months of age (67% from 100%, P<0.05), resulted in smaller tumors at 7 months of age (3.8 cm3 from 7.6 cm3, P=0.003), delayed first tumor appearance (208 days from 188 days, P=0.01), and increased the apoptotic index in the adenocarcinomas (4.3±0.3 from 1.2±0.2, P=0.016). Neither cell proliferation nor differentiation in the cancers was altered. Decreasing Stat5a activation levels could be a therapeutic approach for reducing survival of breast cancer cells.

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Acknowledgements

The authors thank Hallgeir Rui for help with establishing conditions for analysis of Stat5a activity in the adenocarcinomas. DAMD17-98-1-8204 and DAMD17-01-1-0310 supported this work.

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Author notes

  1. Hong Rong Cai

    Present address: Department of Molecular Genetics and Microbiology, UMDNJ, Piscataway, 08854, NJ, USA

Authors and Affiliations

  1. Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, 20007, DC, USA

    Shuxun Ren, Minglin Li & Priscilla A Furth

  2. Department of Medicine, University of Maryland Medical School, Baltimore, 21201, Maryland, MD, USA

    Hong Rong Cai

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  1. Shuxun Ren
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Correspondence to Priscilla A Furth.

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Ren, S., Cai, H., Li, M. et al. Loss of Stat5a delays mammary cancer progression in a mouse model. Oncogene 21, 4335–4339 (2002). https://doi.org/10.1038/sj.onc.1205484

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