Somatic mutation of p53 leads to estrogen receptor α-positive and -negative mouse mammary tumors with high frequency of metastasis

Suh Chin J. Lin, Kuo Fen Lee, Alexander Yu Nikitin, Susan G. Hilsenbeck, Robert Cardiff, Aihua Li, Keon Wook Kang, Steven A. Frank, Wen Hwa Lee, Eva Y.H.P. Lee

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Approximately 70% of human breast cancers are estrogen receptor α (ERα)-positive, but the origins of ERα-positive and -negative tumors remain unclear. Hormonal regulation of mammary gland development in mice is similar to that in humans; however, most mouse models produce only ERα-negative tumors. In addition, these mouse tumors metastasize at a low rate relative to human breast tumors. We report here that somatic mutations of p53 in mouse mammary epithelial cells using the Cre/loxP system leads to ERα-positive and -negative tumors. p53 inactivation under a constitutive active WAPCrec in prepubertal/pubertal mice, but not under MMTVCre in adult mice, leads to the development of ERα-positive tumors, suggesting that target cells or developmental stages can determine ERα status in mammary tumors. Importantly, these tumors have a high rate of metastasis. An inverse relationship between the number of targeted cells and median tumor latency was also observed. Median tumor latency reaches a plateau when targeted cell numbers exceed 20%, implying the existence of saturation kinetics for breast carcinogenesis. Genetic alterations commonly observed in human breast cancer including c-myc amplification and Her2/Neu/erbB2 activation were seen in these mouse tumors. Thus, this tumor system reproduces many important features of human breast cancer and provides tools for the study of the origins of ERα-positive and -negative breast tumors in mice.

Original languageEnglish (US)
Pages (from-to)3525-3532
Number of pages8
JournalCancer Research
Volume64
Issue number10
DOIs
StatePublished - May 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Somatic mutation of p53 leads to estrogen receptor α-positive and -negative mouse mammary tumors with high frequency of metastasis'. Together they form a unique fingerprint.

  • Cite this

    Lin, S. C. J., Lee, K. F., Nikitin, A. Y., Hilsenbeck, S. G., Cardiff, R., Li, A., Kang, K. W., Frank, S. A., Lee, W. H., & Lee, E. Y. H. P. (2004). Somatic mutation of p53 leads to estrogen receptor α-positive and -negative mouse mammary tumors with high frequency of metastasis. Cancer Research, 64(10), 3525-3532. https://doi.org/10.1158/0008-5472.CAN-03-3524