Mechanism of Abnormal Cell-Extracellular Matrix Interactions in Human Breast Cancer.
Abstract
Differential display was exploited to analyze expression patterns of premalignant (S2) and tumor (T4) cells, two sublines of a unique human breast cancer progression HMT3522 series, to identify candidate genes participating in the final-stage tumorigenic conversion in breast cancer. Message levels of a novel gene AZ-i was significantly lower in T4 than in S2 cells cultured either on plastic or in 3-D matrix system. Az-i was abundantly present in nonmalignant counterpart S 1 and human breast luminal epithelial cells. In contrast, expression of this gene was drastically repressed in ten human breast epithelial cancer lines. Modulation of Az-i gene expression by phenotypic alteration of tumor cells was examined in a reversion system described recently in our laboratory. Briefly, when T4 cells were cultured in the presence of inhibitory % 1 -integrin antibody in a 3-D system, they reverted morphologically to S 1-like cells. They formed acini while re-assembled a basement membrane, reorganized cytoskeleton network, suppressed cyclin Di and were growth arrested. Interestingly, AZ-i gene was up-regulated in the reverted T4 cells to a level reminiscent of that seen in the S I cells. Based on the sequence homology with coiled-coil domain of several structural proteins, i.e., myosin heavy chain and desmoplakin I and II, Az-i may play a role in organization of cytoskeletal architecture.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA340571
Entities
People
- Huei-mei Chen
Organizations
- University of California, Berkeley