| Autor: |
K-W Kang, Robert D. Cardiff, AY Nikitin, KM Bushnell, S-Cj Lin, SG Hilsenbeck, Ey-Hp Lee, K-F Lee, W-H Lee, Steven A. Frank, Aihua Li |
| Rok vydání: |
2003 |
| Předmět: |
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| Zdroj: |
Breast Cancer Research : BCR |
| ISSN: |
1465-542X |
| Popis: |
Approximately 70% of human breast cancers are estrogen receptor alpha (ERα)-positive, but the origins of ERα-positive and ERα-negativetumors remain unclear. 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 that somatic mutations of p53 in mouse mammary epithelial cells lead to ERα-positive and ERα-negative tumors. p53 inactivation in pre-pubertal/pubertal mice, but not in adult mice, leads to the development of ERα-positive tumors, suggesting that developmental stages influence the availability of ERα-positive tumor origin cells. These tumors have a high rate of metastasis that is independent of tumor latency. An inverse relationship between the number of targeted cells and median tumor latency was also observed. The 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. Since it is feasible to isolate ERα-positive epithelial cells from normal mammary glands and tumors, molecular mechanisms underlying ERα-positive and ERα-negative mammary carcinogenesis can be systematically addressed using this model. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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