CHARACTERIZATION OF A TRUNCATED PROGESTERONE-RECEPTOR PROTEIN IN BREAST-TUMORS

The progesterone receptor (PR) mediates the actions of progesterone in the normal and malignant breast. PR is expressed as two proteins, PR B and PR A, which are expressed in normal progesterone target tissues and in breast cancers. A significant proportion of breast cancers cont ain, in addition, a smaller PR protein of molecular mass 78 kDa (PR78k Da). The significance of PR78kDa expression is unknown, and in particu lar, there are no data on whether PR78kDa is able to bind ligand and t herefore potentially exhibit transcriptional activity. If this smaller PR species exhibits similar differences in function as have been evid enced in vitro for PR A relative to PR B, it is possible that this PR species may be an important component in determination of progesterone response in breast cancer. The purpose of this study was to determine whether the PR78kDa protein in breast tumors is able to bind ligand a nd to determine whether posttranscriptional mechanisms contribute to i ts formation in breast cancers. There was no evidence that PR78kDa was derived from proteolytic activity of either PR B or PR A. Similarly, although exon-deleted PR transcripts were detected (which could, if tr anslated, give rise to a PR protein similar in size to PR78kDa), neith er the abundance of such transcripts nor their relationship to levels of expressed PR78kDa protein supported a role for exon deletion in for mation of this truncated PR protein. PR78kDa was not recognized by an antibody specific for PR B, indicating that, like PR A, it lacks the N -terminal portion of PR. PR78kDa was able to bind the progestin ligand , indicating that it may have transcriptional activity. In summary, th is study has shown that a truncated PR protein, found in breast cancer s, is ligand-binding and seems to be derived from PR A, indicating tha t it may have a role in progesterone signaling, although a deeper unde rstanding of its role, if any, in breast cancer remains to be establis hed.