MALIGNANCY-SPECIFIC GENE EXPRESSION IN BREAST CANCER

IN 20 TO 40 PERCENT OF HUMAN BREAST CANCERS, THE ERBB-2 OR NEU GENE IS AMPLIFIED, LEADING TO MRNA AND PROTEIN OVEREXPRESSION. AMPLIFICATION OF THE EGF RECEPTOR GENE IS RARE, BUT OVEREXPRESSION OF THE EGF RECEPTOR HAS BEEN SHOWN TO OCCUR WITHOUT ACCOMPANYING GENE AMPLIFICATION. OVEREXPRESSION OF ERBB-2/NEU OR EGF RECEPTOR HAS BEEN LINKED TO A POORER PROGNOSIS FOR THE PATIENT. THIS POORER PROGNOSIS IS LIKELY DUE TO A MORE MALIGNANT POTENTIAL OF CELLS BEARING ERBB-2/NEU OR EGF RECEPTOR OVEREXPRESSION. IN PHASE I, THIS MALIGNANT PHENOTYPE WILL BE EXPLORED BY ISOLATING CDNA'S CORRESPONDING TO MRNA'S WHOSE LEVEL IS MODULATED IN CELLS OVEREXPRESSING ERBB-2/NEU OR EGF RECEPTOR. CDNA LIBRARIES WILL BE SCREENED USING PROBES FROMTHE RNA OF HUMAN TUMOR CELL LINES BEARING ERBB-2/NEU OR EGF RECEPTOR OVEREXPRESSION. CANDIDATE CDNA WILL BE EXAMINED IN A THREE-TIERED SELECTION SYSTEM TO DETERMINE IF THIS CORRESPONDING MRNA IS CONSISTENTLY ALTERED BY OVEREXPRESSIONOF ERBB-2/NEU, EGF RECEPTOR, OR BOTH. IN PHASE II, THE USE OF THESE CDNA'S AS MARKERS OF MALIGNANCY WILL BE EXPLORED, AND THEIR BIOLOGICAL ROLE IN MALIGNANT CONVERSION WILL BE EXAMINED.