Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Breast cancer is one of the most prominent cancers in women with approximately 40,000 women dying each year of the disease in the United States alone. Although cancer has a strong genetic basis, the tissue microenvironment also plays a significant role in tumor formation and progression. To explore this process in greater detail, we analyzed tissue structure, cellular biochemistry and gene expression change during tumor progression in a previously developed FVB C3(1)-SV40Tag transgenic mouse model in which the females spontaneously develop mammary tumors that undergo changes in cell tissue morphology that closely mimic those observed during human breast cancer progression. Histological characterization of breast tissues isolated from 8, 12, 16 and 20 week old female mice confirmed that this model is extremely robust with normal glandular morphology being observed at 8 weeks, ductal carcinoma in situ (DCIS) morphology appearing at 12 weeks and 16 weeks and large tumors with metastatic lesions by 20 weeks of age. More careful analysis revealed that tumor formation did not scale directly with expression of SV40 large T antigen that is the drive gene in this transgenic model, and instead appeared to be more closely related to variations in the tissue microenvironment. This was supported by the observation that the number of myoepithelial cells and expression levels of known breast cancer differentiation markers, including estrogen and progesterone receptors, varied among ducts within tissues at each time point even though the majority of epithelial cells in these ducts expressed T antigen. Gene microarray analysis of mammary tissues from these time points revealed consistent changes in genome-wide expression profiles, and several interesting candidates are currently being analyzed regarding their potential involvement in early microenvironmental changes that might drive the tumor progression. In summary, our preliminary results showed that despite expression of constitutively active large T antigen in the breast epithelial cells of these transgenic mice, we observe heterogeneous tumor formation within mammary tissues. These local variations in tumor progression may be related to regional changes in stromal and extracellular matrix components that are currently being analyzed by immunohistochemical analysis. Our long-term goal is to leverage the information we uncover through this effort to design differentiation therapies that suppress tumor cell growth, induce differentiation and hence, reverse breast cancer progression.</jats:p>
<jats:p>Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 520. doi:10.1158/1538-7445.AM2011-520</jats:p>