Loss of B-cell translocation gene-2 in estrogen receptor-positive breast carcinoma is associated with tumor grade and overexpression of cyclin d1 protein.
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.
Kawakubo
Hirofumi
H
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Brachtel
Elena
E
Hayashida
Tetsu
T
Yeo
Giminna
G
Kish
Joshua
J
Muzikansky
Alona
A
Walden
Paul D
PD
Maheswaran
Shyamala
S
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
D047628:Estrogen Receptor alpha; D017874:Immediate-Early Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; C070114:BTG2 protein, human