Her-2/Neu and Breast Cancer.
Annual rept. 8 Jul 95-7 Jul 96,
OREGON UNIV HEALTH SCIENCES CENTER PORTLAND
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The HER-2neu c-erbB2 protooncogene is overexpressed in up to 30 of breast and ovarian cancers. Overexpression as a 185 kilodalton transmembrane growth-factor-receptortyrosine-kinase pl85HER2 is an indicator of poor prognosis. Attempting to characterize the significance of alternative forms of pl85HER2, I have focussed on a truncated p95 form comprising the transmembrane and tyrosine kinase domains, and more recently, on an alternative transcript. Specifically, the SKOV-3 carcinoma cell line highly overexpresses HER-2 neu protein and expresses an aberrant HER-2 neu transcript of 8 kb, in addition to the normal 4.5 kb transcript. This larger transcript may be the product of a gene rearrangement, as SKOV-3 cells exhibit amplification of the HER-2neu gene, and Southern blotting experiments indicate a gene rearrangement. Current studies are aimed at characterizing this aberrant HER-2neu transcript in terms of quantification, sequence analysis, and identifying its significance in overexpression of HER-2neu protein. Since this transcript seems to be selected for in the malignant SKOV-3 cell line, it may confer enhanced oncogenic potential.
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