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 presence of several exon-deleted PR variant mRNAs in both normal and neoplastic breast samples has recently been reported. Amongst them, a variant mRNA deleted in exon 6 (D6-PR mRNA) that if translated would encode a truncated PR-like protein missing the hormone binding domain and one of the transactivating domains of the wild-type PR protein. In order to determine whether changes in D6-PR variant expression could occur during tumorigenesis, its expression was investigated by reverse transcription and polymerase chain reaction in ten normal reduction mammoplasty samples, nine breast tumours with high PR levels (> 100 fmol mg(-1) protein) and eight breast tumours with low PR levels (< 15 fmol mg(-1) protein), as determined by ligand binding assay. The relative expression of D6-PR to wild-type PR mRNA was lower (P< 0.01 ) in normal than in all tumour breast samples. Moreover, a trend to lower (P < 0.1) relative D6-PR expression was observed in high PR tumours, compared to low PR tumours. These data suggest that increased expression of D6-PR occurs during tumorigenesis.
Department of Biochemistry and Molecular Biology, University of Manitoba, Faculty of Medicine, Winnipeg, Canada.
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E
Leygue
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Dotzlaw
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PH
Watson
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LC
Murphy
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics*; D012016:Reference Values
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011980:Receptors, Progesterone