[논문]Somatic Mutation of p53 Leads to Estrogen Receptor α-Positive and -Negative Mouse Mammary Tumors with High Frequency of Metastasis

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

doi:10.1158/0008-5472.can-03-3524

Somatic Mutation of p53 Leads to Estrogen Receptor α-Positive and -Negative Mouse Mammary Tumors with High Frequency of Metastasis 원문보기

Cancer research : the official organ of the American Association for Cancer Research, Inc, v.64 no.10, 2004년, pp.3525 - 3532

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

Abstract ▼ AI-Helper

AbstractApproximately 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.

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Somatic Mutation of p53 Leads to Estrogen Receptor α-Positive and -Negative Mouse Mammary Tumors with High Frequency of Metastasis 원문보기

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