COEXPRESSION OF WILD-TYPE AND VARIANT ESTROGEN-RECEPTOR MESSENGER-RNAS IN A PANEL OF HUMAN BREAST-CANCER CELL-LINES

Wild-type as well as variant oestrogen receptor (ER) mRNAs with exon 5 and 7 deleted were identified in a panel of human breast tumour cell lines by reverse transcriptase-polymerase chain reaction followed by d ideoxynucleotide sequence analysis, and then quantitated by ribonuclea se protection analysis. All cell lines categorised as ER(+) by ligand- binding analysis expressed both wild-type and variant ER transcripts. Most cell lines classified as ER(-) did not express any ER transcript. However, three ER cell lines (BT-20, MDA-MB-330 and T47D(co)) express ed both wild-type and variant transcripts. A differential pattern of e xpression of wild type to variant was seen in both ER(+) and ER(-) cel l lines, however this pattern was not paralleled by differences in lig and-binding activity. Breast tumour cell lines previously classified a s ER(-) expressed significantly lower levels of ER transcripts than di d their ER(+) counterparts. In view of these findings, as well as earl ier reports that the exon 5 deletion ER variant encodes a dominant-pos itive receptor, it seems clear that some cell lines are misclassified as ER(-), and express both wild-type and variant ER mRNAs, and that th e overexpression of this variant may account, in part, for their oestr ogen-independent phenotype.