title: Expression of a novel splicing variant deleting exons 4 and 6 of the progesterone receptor gene is a rare event in breast cancer.
abstract: We identified a novel alternatively spliced isoform of PR mRNA in breast cancer tissues. The deleted transcript was characterized by an out-of-frame deletion of 437 bp, corresponding to the complete loss of exons 4 and 6 (PR delta4+6 ASV). PR delta4+6 ASV will result in a partial defect in the region of the ligand-binding domain of hormone receptors, suggesting that the conserved residues are missing from the core of the protein. In the limited number of samples studied, a novel PR delta4+6 mRNA was detected in 1 of 45 (2.2%) non-cancerous tissues of patients with breast cancer, in 5 of 45 (11.1%) cancerous tissues of patients with breast cancer. Loss of both exons 4 and 6 will be induced by incomplete splicing and/or repair mechanism. Further studies are necessary to establish the biological significance of this alternative splicing. The expressions of ASVs that induced the mimic PR transcripts need to be considered when designing strategies for regulation analysis of the PR gene.
authors.affiliation: Center for Molecular Biology and Cytogenetics, SRL, Inc, Tokyo 191-0002, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Nagao
authors.forename: Norio
authors.initials: N
authors.lastname: Kohno
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Wakita
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hikiji
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hisatomi
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007564:Japan; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011980:Receptors, Progesterone