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 dideoxynucleotide sequence analysis, and then quantitated by ribonuclease 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)) expressed both wild-type and variant transcripts. A differential pattern of expression of wild type to variant was seen in both ER(+) and ER(-) cell lines, however this pattern was not paralleled by differences in ligand-binding activity. Breast tumour cell lines previously classified as ER(-) expressed significantly lower levels of ER transcripts than did their ER(+) counterparts. In view of these findings, as well as earlier reports that the exon 5 deletion ER variant encodes a dominant-positive receptor, it seems clear that some cell lines are misclassified as ER(-), and express both wild-type and variant ER mRNAs, and that the overexpression of this variant may account, in part, for their oestrogen-independent phenotype.