title: GSK3β and cyclin D1 expression predicts outcome in early breast cancer patients.
abstract: Glycogen synthase kinase 3β (GSK3β) is phosphorylated and inactivated by the phosphoinositide 3 kinase PI3K/Akt pathway. Activation of Akt phosphorylates GSK3β preventing phosphorylation of cyclin D1 which leads to accumulation and nuclear localisation of cyclin D1, activation of CDK4/6 and cell cycle progression. The CCND1 gene found at chromosome 11q13 has been shown to be amplified in approximately 15 % of breast cancers. Cyclin D1, the product of the CCND1 gene, is one of the most commonly overexpressed proteins in breast cancer. Protein expression for GSK3β, phosphorylated-GSK3β (p-GSK3β), cyclin D1 and gene expression of CCND1 were examined in tissue microarrays of 1,686 patients from the Edinburgh Breast Conservation Series. High GSK3β expression was associated with reduced distant relapse-free survival (DRFS), while no association between p-GSK3β and breast cancer-specific survival was seen. CCND1 amplification is also associated with poor DRFS. On the contrary, cyclin D1 overexpression is associated with an increase in DRFS. Multivariate analysis was performed. We suggest that analysis of both GSK3β and cyclin D1 expressions can be considered as a marker of good prognosis in early breast cancer.
authors.affiliation: Endocrine Cancer Group, Edinburgh University, Edinburgh, UK.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Quintayo
authors.forename: Alison F
authors.initials: AF
authors.lastname: Munro
authors.forename: Jeremy
authors.initials: J
authors.lastname: Thomas
authors.forename: Ian H
authors.initials: IH
authors.lastname: Kunkler
authors.forename: Wilma
authors.initials: W
authors.lastname: Jack
authors.forename: Gillian R
authors.initials: GR
authors.lastname: Kerr
authors.forename: J M
authors.initials: JM
authors.lastname: Dixon
authors.forename: Udi
authors.initials: U
authors.lastname: Chetty
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013629:Tamoxifen / Q000008:administration & dosage; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D013629:Tamoxifen; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3