Loss of cyclin D2 expression in the majority of breast cancers is associated with promoter hypermethylation

Cyclin D2 is a member of the D-type cyclins, implicated in cell cycle regulation, differentiation, and malignant transformation. It was noted previously that cyclin D2 is not expressed in the majority of breast cancer cell lines, whereas abundant expression was detected in finite life span human mam...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-03, Vol.61 (6), p.2782-2787
Main Authors: EVRON, Ella, UMBRICHT, Christopher B, KORZ, Dorian, RAMAN, Venu, LOEB, David M, NIRANJAN, Birunthi, BULUWELA, Lakjaya, WEITZMAN, Sigmund A, MARKS, Jeffrey, SUKUMAR, Saraswati
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blotting, Western
Breast - cytology
Breast - metabolism
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Carcinoma in Situ - genetics
Carcinoma in Situ - metabolism
Carcinoma, Ductal, Breast - genetics
Carcinoma, Ductal, Breast - metabolism
CpG Islands
Cyclin D2
Cyclins - biosynthesis
Cyclins - genetics
DNA Methylation
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Gynecology. Andrology. Obstetrics
Humans
hypermethylation
Mammary gland diseases
Medical sciences
Promoter Regions, Genetic
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Tumors
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Summary:Cyclin D2 is a member of the D-type cyclins, implicated in cell cycle regulation, differentiation, and malignant transformation. It was noted previously that cyclin D2 is not expressed in the majority of breast cancer cell lines, whereas abundant expression was detected in finite life span human mammary epithelial cells. By reverse transcription-PCR and Western blot analysis, we extended this finding to primary breast carcinomas and show that the majority of these tumors lack expression of cyclin D2 mRNA (18 of 24) and protein (10 of 13). In contrast, both luminal and myoepithelial subpopulations of normal breast tissues expressed cyclin D2. Hypermethylation of the CpG island in the promoter was detected by methylation-specific PCR in nearly half of the breast cancers (49 of 106) and was associated with silencing of cyclin D2 gene expression. Promoter hypermethylation was also detected in ductal carcinoma in situ, suggesting that loss of cyclin D2 expression is an early event in tumorigenesis. Our results suggest that loss of cyclin D2 expression is associated with the evolution of breast cancer.
ISSN:0008-5472
1538-7445