Progesterone receptor isoforms

Another field of future investigation is to decipher the functional importance of the altered expression of PR isoforms and how this may affect the response of breast tumors to endocrine therapy. PR is expressed as two iso-forms - PR-A and PR-B, which are products of a single gene but which are under the control of two distinct promoters.116 The two isoforms possess different, promoter- and cell line-specific transactivation properties. Studies have shown that in poor prognostic tumors, the ratio between PR-A and PR-B is altered, with PR-A predominating and loss of PR-B.117 An overabundance of PR-A may be associated with resistance to tamoxifen,117 while functional polymorphism resulting in increased production of PR-B may be associated with an increased risk of breast cancer.118 Other findings showed that PR-B expression was correlated with good prognostic markers and better overall survival in breast cancer.119 In a study of T47D human breast tumor xeno-grafts, tamoxifen preferentially inhibited the growth of PR-A tumors, whereas PR-B tumors were unaffected.120 Recently, PR-A and PR-B were both found to be predictive of response to endocrine therapy.66 Taken together, these findings highlight the need for future studies to decipher the functional importance of the altered expression of PR isoforms and how disrupted progesterone signaling may affect the response of breast tumors to endocrine therapy.

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