Pathways Contributing to Development of Spontaneous Mammary Tumors in BALB/c-Trp53+/− Mice
| Autor: | Barbara A. Osborne, Ellen S. Dickinson, Richard B. Arenas, Elizabeth A. Xavier, D. Joseph Jerry, Rebecca G. Lawlor, Frances S. Kittrell, Qing J. Cao, Jae Hong Seo, Daniel Medina, Haoheng Yan, S. Christine McLary, Christopher N. Otis, Amy L. Roberts, Anneke C. Blackburn, Luwei Tao |
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| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty Receptor ErbB-2 animal diseases Mammary gland Loss of Heterozygosity Estrogen receptor Mammary Neoplasms Animal Pathology and Forensic Medicine BALB/c Loss of heterozygosity Mice Cancer stem cell Progesterone receptor medicine Animals Mice Inbred BALB C Receptors Notch biology Mammary Neoplasms Experimental biology.organism_classification Gene Expression Regulation Neoplastic Transplantation medicine.anatomical_structure Receptors Estrogen Cancer research Keratins Female Tumor Suppressor Protein p53 Receptors Progesterone Precancerous Conditions Estrogen receptor alpha Neoplasm Transplantation Regular Articles Signal Transduction |
| Zdroj: | The American Journal of Pathology. 176:1421-1432 |
| ISSN: | 0002-9440 |
| Popis: | Mutation and loss of function in p53 are common features among human breast cancers. Here we use BALB/c-Trp53+/- mice as a model to examine the sequence of events leading to mammary tumors. Mammary gland proliferation rates were similar in both BALB/c-Trp53+/- mice and wild-type controls. In addition, sporadic mammary hyperplasias were rare in BALB/c-Trp53+/- mice and not detectably different from those of wild-type controls. Among the 28 mammary tumors collected from BALB/c-Trp53+/- mice, loss of heterozygosity for Trp53 was detected in more than 90% of invasive mammary tumors. Transplantation of Trp53+/- ductal hyperplasias also indicated an association between loss of the wild-type allele of Trp53 and progression to invasive carcinomas. Therefore, loss of p53 function seems to be a rate-limiting step in progression. Moreover, expression of biomarkers such as estrogen receptor alpha, progesterone receptor, Her2/Neu, and activated Notch1 varied among mammary tumors, suggesting that multiple oncogenic lesions collaborate with loss of p53 function. Expression of biomarkers was retained when tumor fragments were transplanted to syngeneic hosts. Tumors expressing solely luminal or basal keratins were also observed (27 and 11%, respectively), but the largest class of tumors expressed both luminal and basal keratins (62%). Overall, this panel of transplantable tumors provides a resource for detailed evaluation of the cell lineages undergoing transformation and preclinical testing of therapeutic agents targeting a variety of oncogenic pathways including cancer stem cells. |
| Databáze: | OpenAIRE |
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