title: Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein.
abstract: The B-cell translocation gene-2 (BTG2) is present in the nuclei of epithelial cells in many tissues, including the mammary gland where its expression is regulated during glandular proliferation and differentiation in pregnancy. In immortalized mammary epithelial cells and breast cancer cells, BTG2 protein localized predominantly to the nucleus and cytoplasm, respectively. The highly conserved domains (BTG boxes A, B, and C) were required for regulating localization, suppression of cyclin D1 and growth inhibitory function of BTG2. Expression analysis of BTG2 protein in human breast carcinoma (n = 148) revealed the loss of nuclear expression in 46% of tumors, whereas it was readily detectable in the nuclei of adjacent normal glands. Loss of nuclear BTG2 expression in estrogen receptor-alpha (ERalpha)-positive breast tumors correlated significantly with increased histologic grade and tumor size. Consistent with its ability to suppress cyclin D1 transcription, loss of nuclear BTG2 expression in ER-positive breast carcinomas showed a significant correlation with cyclin D1 protein overexpression, suggesting that loss of BTG2 may be a factor involved in deregulating cyclin D1 expression in human breast cancer.
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawakubo
authors.forename: Elena
authors.initials: E
authors.lastname: Brachtel
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayashida
authors.forename: Giminna
authors.initials: G
authors.lastname: Yeo
authors.forename: Joshua
authors.initials: J
authors.lastname: Kish
authors.forename: Alona
authors.initials: A
authors.lastname: Muzikansky
authors.forename: Paul D
authors.initials: PD
authors.lastname: Walden
authors.forename: Shyamala
authors.initials: S
authors.lastname: Maheswaran
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins
chemical_list: D047628:Estrogen Receptor alpha; D017874:Immediate-Early Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; C070114:BTG2 protein, human