ESTROGEN-RECEPTOR VARIANTS IN CLINICAL BREAST-CANCER

We have used the screening techniques of chemical mismatch cleavage, single stranded conformational polymorphism, and gel retardation to discover a number of estrogen receptor RNA variants in clinical breast cancer tissues. We have found basepair insertions, transitions, and deletions as well as alternative splicing, yielding deletions of exon 3, 5, or 7. Using a yeast transactivation assay we have discovered receptors with outlaw function, including both a dominant-positive receptor, which is transcriptionally active in the absence of estrogen, and a dominant-negative receptor, which is itself transcriptionally inactive, but prevents the action of normal estrogen receptor. These variants could have clinical significance, helping to explain breast tumor behavior and patient outcome.