title: Novel alternatively spliced variant with a deletion of 52 BP in exon 6 of the progesterone receptor gene is observed frequently in breast cancer tissues.
abstract: The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor that mediates progesterone action in target tissues. We found a novel alternatively spliced variant (ASV) of the PR mRNA in breast cancer tissues. The deleted transcript was characterized by an out-of-frame deletion of 52 bp in exon 6 (PR delta6/2 ASV). The PR delta6/2 ASV mRNA results in a partial defect in the region of the ligand-binding domain of the hormone receptor, where conserved residues are missing from the core of the protein. To clarify the clinical significance of the PR delta6/2 ASV, we investigated the expression of this ASV in noncancerous and cancerous tissues from patients with breast cancer using RT-PCR. The novel PR delta6/2 mRNA was detected in 24 of 39 (61.5%) cancerous tissues and in 3 of 39 (7.7%) noncancerous tissues from patients with breast cancer. PR delta6/2 ASV mRNA was expressed more frequently in breast cancer tissues than in noncancerous tissues (p < 0.0001), which suggests a possible relationship between the expression of PR delta6/2 and breast cancer. Our observations may provide a novel strategy for the genetic diagnosis of breast cancer.
authors.affiliation: Center for Molecular Biology and Cytogenetics, SRL Inc., Tokyo, Japan. hisatomi@srl.srl-inc.co.jp
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hisatomi
authors.forename: Norio
authors.initials: N
authors.lastname: Kohno
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Wakita
authors.forename: Kumi
authors.initials: K
authors.lastname: Nagao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirata
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hikiji
authors.forename: Shoji
authors.initials: S
authors.lastname: Harada
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; 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
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011980:Receptors, Progesterone