Restoration of Epithelial Polarity in Metastatic Tumors
Final rept. 1 Jul 2005-30 Jun 2006
MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
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Malignant properties of breast cancer cells are known to depend on their altered polarity and adhesion properties. LGL genes function by controlling normal epithelial polarity and suppressing tumors in the fruit fly. The LGL proteins were also proposed to decrease the frequency of epithelial tumor formation in mammals. To test this idea, we monitored LGL expression in epithelial cells undergoing malignant transformation to correlate it with increased cell motility and altered cell shape. Whereas we found that LGL1 protein is present in most cell lines analyzed, we attempted to restore proper cell adhesion and epithelial organization of breast carcinoma cell lines by genetic manipulation of the LGL gene. We observed that the proliferation of carcinoma cell lines with increased expression of LGL1 has been suppressed, consistent with the hypothesis that LGL1 may function as a tumor suppressor. Our experiments may allow the design of physiologically relevant drugs against breast cancer.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology