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Characterization of a Truncated Progesterone Receptor Protein in Breast Tumors¹

Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia

Address all correspondence and requests for reprints to: Dr. C. L. Clarke, Department of Medical Oncology, Westmead Hospital, Westmead, NSW 2145, Australia. E-mail: chrisc{at}westmed.wh.su.edu.au

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 contain, in addition, a smaller PR protein of molecular mass 78 kDa (PR78kDa). The significance of PR78kDa expression is unknown, and in particular, there are no data on whether PR78kDa is able to bind ligand and therefore potentially exhibit transcriptional activity. If this smaller PR species exhibits similar differences in function as have been evidenced 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 and to determine whether posttranscriptional mechanisms contribute to its 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 translated, give rise to a PR protein similar in size to PR78kDa), neither the abundance of such transcripts nor their relationship to levels of expressed PR78kDa protein supported a role for exon deletion in formation 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, this study has shown that a truncated PR protein, found in breast cancers, is ligand-binding and seems to be derived from PR A, indicating that it may have a role in progesterone signaling, although a deeper understanding of its role, if any, in breast cancer remains to be established.

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