Coexpression of wild-type and variant oestrogen receptor mRNAs 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 T47Dco) 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.
Castles
C G
CG
Department of Medicine/Oncology, University of Texas Health Science Center at San Antonio 78284, USA.
Klotz
D M
DM
Fuqua
S A
SA
Hill
S M
SM
D001483:Base Sequence; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure*; D003001:Cloning, Molecular; D005091:Exons; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000648:ultrastructure*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D008024:Ligands; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D012260:Ribonucleases