Variant estrogen receptor-alpha messenger RNA expression in hormone-independent human breast cancer cells

T5-PRF cells are insensitive to the growth-stimulatory effects of estrogen while still retaining expression of estrogen receptor-alpha (ER-alpha). In the apparent absence of ligand, T5-PRF cells have a 3.6 +/- 0.5 (S.E.M.)-fo ld increased basal ER-alpha activity and elevated basal progesterone recept or levels compared with the parent, estrogen-sensitive, T5 cells. Long-rang e ER-alpha reverse transcription-PCR was performed to characterize variant ER-alpha mRNA expression in the two cell lines. An increased relative expre ssion of an exon 3/4-deleted ER-alpha mRNA variant was found in T5-PRF. Rec ombinant expression of this ER-alpha variant resulted in significantly incr eased estrogen responsiveness, as well as a trend to increased basal ligand -independent activity when expressed with wild-type ER-alpha in ER-negative cell lines, as well as significantly increasing both ligand-independent an d estrogen-induced ER-alpha transcriptional activity when expressed in pare ntal T5 cells. These results suggest a role for altered variant ER-alpha in ligand-independent activation of ER-alpha which may contribute to hormone independence in breast tumors.