Altered expression of exon 6 deleted progesterone receptor variant mRNA between normal human breast and breast tumour tissues

The progesterone receptor (PR) is an important prognostic marker in breast cancer as well as a marker of responsiveness to endocrine therapies. The pr esence of several exon-deleted PR variant mRNAs in both normal and neoplast ic breast samples has recently been reported. Amongst them, a variant mRNA deleted in exon 6 (DG-PR mRNA) that ii translated would encode a truncated PR-like protein missing the hormone binding domain and one of the transacti vating domains of the wild-type PR protein. In order to determine whether c hanges in DG-PR variant expression could occur during tumorigenesis, its ex pression was investigated by reverse transcription and polymerase chain rea ction in ten normal reduction mammoplasty samples, nine breast tumours with high PR levels (> 100 fmol mg(-1) protein) and eight breast tumours with l ow PR levels (< 15 fmol mg(-1) protein), as determined by ligand binding as say. The relative expression of DG-PR to wild-type PR mRNA was lower (P < 0 .01) in normal than in all tumour breast samples. Moreover, a trend to lowe r (P < 0.1) relative DG-PR expression was observed in high PR tumours, comp ared to low PR tumours. These data suggest that increased expression of DG- PR occurs during tumorigenesis.