RGD Reference Report - Hypermethylation of Cyclin D2 is associated with loss of mRNA expression and tumor development in prostate cancer. - Rat Genome Database

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Hypermethylation of Cyclin D2 is associated with loss of mRNA expression and tumor development in prostate cancer.

Authors: Henrique, R  Costa, VL  Cerveira, N  Carvalho, AL  Hoque, MO  Ribeiro, FR  Oliveira, J  Teixeira, MR  Sidransky, D  Jeronimo, C 
Citation: Henrique R, etal., J Mol Med. 2006 Nov;84(11):911-8. Epub 2006 Sep 22.
RGD ID: 2289151
Pubmed: PMID:17016690   (View Abstract at PubMed)
DOI: DOI:10.1007/s00109-006-0099-4   (Journal Full-text)

D-type cyclins play a pivotal role in cell cycle regulation and their abnormal expression was associated with several human malignancies. To assess Cyclin D2 promoter methylation status and expression levels in prostate tissues, quantitative methylation-specific PCR and quantitative reverse transcription PCR assays were performed in a large series of prostate carcinomas, high-grade prostatic intraepithelial neoplasias (HGPIN), benign prostate hyperplasias (BPH), normal prostate tissue (NPT) samples, and prostate cancer (PCa) cell lines (before and after demethylating treatment). Methylation levels were correlated with mRNA expression levels and key clinicopathologic parameters. Cyclin D2 promoter methylation was found in 117/118 PCa, 38/38 HGPIN, 24/30 BPH, 11/11 NPT, and 4/4 cell lines. Methylation levels were significantly higher in PCa compared with HGPIN, NPT, and BPH (P<0.0001), correlating with tumor stage and Gleason score (r=0.29, P=0.0014; and r=0.32, P=0.0005, respectively). Conversely, Cyclin D2 mRNA levels were significantly lower in PCa (P<0.01) and a significant inverse correlation between Cyclin D2 methylation and expression levels was found in prostatic tissues (r=-0.61, P<0.000001). Demethylating treatment induced a substantial increase in Cyclin D2 mRNA in LNCaP cells whereas decreased levels were observed in DU-145 and PC-3 cells. We concluded that Cyclin D2 promoter methylation downregulates gene transcription and occurs with high frequency at low levels in normal, hyperplastic, and preneoplastic prostate tissues. Conversely, high Cyclin D2 methylation levels characterize invasive prostatic carcinoma, correlating with clinicopathologic features of tumor aggressiveness.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCND2Humanprostate cancer  IDA DNA more ...RGD 
Ccnd2Ratprostate cancer  ISOCCND2 (Homo sapiens)DNA more ...RGD 
Ccnd2Mouseprostate cancer  ISOCCND2 (Homo sapiens)DNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccnd2  (cyclin D2)

Genes (Mus musculus)
Ccnd2  (cyclin D2)

Genes (Homo sapiens)
CCND2  (cyclin D2)


Additional Information