Characterization of Novel Seven Transmembrane Helix, GS-Coupled Receptors and Pou Domain Proteins in Cancer of the Mammary Epithelium

Understanding the molecular basis of breast carcinoma is central to designing rational and effective therapy for this prevalent disease. We have proposed to investigate several regulatory proteins that we hypothesized may underlie at least a subset of human breast carcinomas. In investigating transcription factors of the POU domain class and their synergistic interactions with nuclear receptors, we have discovered a novel protein, expressed in the breast, that acts as a specific repressor of retinoic acid and thyroid hormone receptors. This 270 kDa protein, postulated to mediate retinoic acid and thyroid hormone receptor actions as a repressor of specific gene expression, is recruited to estrogen receptor by antagonists and its regulation appears to underlie resistance in ER positive tumors.