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 protein is a 270kDa protein that is postulated to mediate retinoic acid and thyroid hormone receptor actions as a repressor of specific gene expression. We now have additionally identified a breast-specific form of a co-activator and estrogen and the role of the CREB binding protein in nuclear receptor interaction. These molecules are thus candidates for initiating events in breast tumors. The co-repressor and co-activato and co-integrator proteins together are hypothesized to control mmmmalian cell proliferation, and the maintenance of mature cell phenotypes, and represent intriguing candidates for involvement in initiation of tumor events.