title: An exon 5 deletion variant of the estrogen receptor frequently coexpressed with wild-type estrogen receptor in human breast cancer.
abstract: Recent evidence suggests that the expression of estrogen receptor (ER) variants in breast cancer may interfere with wild-type (wt) ER function and be related to tumor progression and resistance to hormone treatment. One of these variants, ER delta E5, lacking that part of the hormone-binding domain encoded by exon 5, has previously been identified in breast tumors with the unusual estrogen receptor negative (ER-) and progesterone receptor positive (PgR+) phenotype and found to possess constitutive and hormone-independent transcriptional activity. Using a ribonuclease protection assay, we analyzed 27 breast tumors and 4 breast cell lines for the presence of this variant. We found the ER delta E5 variant to be expressed, not only in all of three ER-/PgR+ tumors but also in 19 of 20 ER+/PgR+ or ER+/PgR- tumors. Moreover, the variant was always coexpressed with and often in excess of wtER. ER delta E5 was also found in three breast cancer cell lines (MCF7, T47D, and ZR75-1), although to a lesser extent than wtER. A complete absence of both ER delta E5 and wtER was noted in four ER-/PgR- tumors and one normal breast cell line (HBL-100). Thus, our data suggest that the occurrence of ER delta E5 in breast cancer may represent a critical stage in tumor progression to autonomy.
authors.affiliation: Department of Oncology, University Hospital, Lund, Sweden.
authors.forename: Q X
authors.initials: QX
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: S A
authors.initials: SA
authors.lastname: Fuqua
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D010641:Phenotype; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone