Breast Cancer in Context: New Tools and Paradigms for the Millennium
Annual rept. 1 Jul 2005-30 Jun 2006
CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
Pagination or Media Count:
We hypothesize that breast tumors are capable of multiple differentiation pathways. A finite number of interconnected pathways establish homeostasis in normal tissues which, if still functional in tumors, may be manipulated. Our goal is to characterize -51 breast cancer cell lines with known genomic profiles utilizing a robust 3-dimensional assay with laminin-rich extracellular matrix 3D IrECM. In this assay non-malignant mammary epithelial cells form acinar structures whereby cells growth arrest, polarize and form a central lumen while tumorigenic cells continue to proliferate and form a disorganized mass. In this assay, treatment of tumorigenic cells with various signaling inhibitors alone or in combination phenotypically reverts or kills cancer cells. To date, the majority of the tumor lines have been obtained and grouped according to their morphology in 3D IrECM. Refined analysis identified six distinct morphologies termed round, round mass, irregular mass, grape-like, grape-like stellate and invasive stellate. Twenty-six cell lines have been characterized by gene expression and proteomic profiles of selected signaling pathways. We are analyzing these expression profiles to identify common signaling themes andor morphological regulators as well as performing studies correlating morphology and expression profiles with response to Herceptin and other therapeutic agents.
- Anatomy and Physiology
- Medicine and Medical Research