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Mammary Tumors Initiated by Constitutive Cdk2 Activation Contain an Invasive Basal-like Component
- Source :
- Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 11, Pp 1240-1252 (2008)
- Publication Year :
- 2008
- Publisher :
- Elsevier, 2008.
-
Abstract
- The basal-like subtype of breast cancer is associated with invasiveness, high rates of postsurgical recurrence, and poor prognosis. Aside from inactivation of the BRCA1 tumor-suppressor gene, little is known concerning the mechanisms that cause basal breast cancer or the mechanisms responsible for its invasiveness. Here, we show that the heterogeneous mouse mammary tumor virus-cyclin D1-Cdk2 (MMTV-D1K2) transgenic mouse mammary tumors contain regions of spindle-shaped cells expressing both luminal and myoepithelial markers. Cell lines cultured from these tumors exhibit the same luminal/myoepithelial mixed-lineage phenotype that is associated with human basal-like breast cancer and express a number of myoepithelial markers including cytokeratin 14, P-cadherin, α smooth muscle actin, and nestin. The MMTV-D1K2 tumor-derived cell lines form highly invasive tumors when injected into mouse mammary glands. Invasion is associated with E-cadherin localization to the cytoplasm or loss of E-cadherin expression. Cytoplasmic E-cadherin correlates with lack of colony formation in vitro and β-catenin and p120ctn localization to the cytoplasm. The data suggest that the invasiveness of these cell lines results from a combination of factors including mislocalization of E-cadherin, β-catenin, and p120ctn to the cytoplasm. Nestin expression and E-cadherin mislocalization were also observed in human basal-like breast cancer cell lines, suggesting that these results are relevant to human tumors. Together, these results suggest that abnormal Cdk2 activation may contribute to the formation of basal-like breast cancers.
- Subjects :
- Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Subjects
Details
- Language :
- English
- ISSN :
- 14765586 and 15228002
- Volume :
- 10
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Neoplasia: An International Journal for Oncology Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.1367d8fff5c47468a334ed828a08839
- Document Type :
- article
- Full Text :
- https://doi.org/10.1593/neo.08710