Regulation of the Multidrug Resistance-Associated Protein Gene by Estrogen.

摘要

An observation was made that the mRNAs for two clones, number 41 and number 44, were rapidly repressed by estrogen in chick oviduct. Clone number 44 shared sequence homology with members of the multidrug resistance-associated protein (mrp) gene family. This raised the question of whether the multidrug resistance (mdr) phenotype in breast cancer may be in part due to the loss of repression of MRP expression by estrogen when antiestrogens are administered. The goals of this last year were to complete the identification of clone number 41 and to publish a manuscript describing the work completed thus far. The latter goal has been accomplished and is included as Appendix A. The results with MRP1 have considerable significance in light of two recent reports that indicate that MRP mRNA is highly expressed in primary breast cancers, particularly those with poor prognosis. Our observations raise the possibility that one or more of the selective estrogen receptor modulators (SERMs) may be useful in treating those resistant cancers. While we do not as yet have the complete sequence of clone number 41, about 1,000 new bp of sequence has been obtained. The (caret)1300 bp in hand encodes a predicted protein with about 96% identity to two human and one mouse partial clones of the kelch superfamily.