RGD Reference Report - Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma. - Rat Genome Database

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Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma.

Authors: Zhu, C  Qin, YR  Xie, D  Chua, DT  Fung, JM  Chen, L  Fu, L  Hu, L  Guan, XY 
Citation: Zhu C, etal., Oncogene. 2009 Aug 6;28(31):2821-8. doi: 10.1038/onc.2009.137. Epub 2009 Jun 15.
RGD ID: 9590307
Pubmed: PMID:19525977   (View Abstract at PubMed)
DOI: DOI:10.1038/onc.2009.137   (Journal Full-text)

Deletion of 3p is one of the most frequent genetic alterations in many tumors, including esophageal squamous cell carcinoma (ESCC). In our recent study, deletion of 3p24 was frequently detected in ESCC and one candidate tumor suppressor gene (TSG), p300/CBP-associated factor (PCAF), was identified within the region. In this study, downregulation of PCAF was detected in 23/40 (57.5%) of primary ESCCs and 4/9 (44.4%) of the ESCC cell lines. A further study found that downregulation of PCAF was also associated with hypermethylation of the promoter region of PCAF gene. Methylation-specific PCR found that promoter methylation was detected in 28/40 (70%) of primary ESCCs and 5/9 (55.6%) of ESCC cell lines. In addition, the expression of PCAF could be reactivated in ESCC cell line KYSE510 after demethylation treatment with 5-aza-dC. Functional studies showed that PCAF was able to suppress tumorigenicity of ESCC cells both in vitro and in vivo, including foci formation, colony formation in soft agar and tumor formation in nude mice. Molecular study found that the tumor suppressive mechanism of PCAF was associated with its role in cell cycle arrest at the G1/S checkpoint by the downregulation of CDK2 and upregulation of p21(waf1/Cip1), Smad4, Rb and p27(Kip1). In conclusion, PCAF might be the target TSG responsible for the 3p24 deletion event, which has an important role in the development and progression of ESCC.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KAT2BHumanesophagus squamous cell carcinoma  IEP mRNA:decreased expression:esophagus (human)RGD 
Kat2bRatesophagus squamous cell carcinoma  ISOKAT2B (Homo sapiens)mRNA:decreased expression:esophagus (human)RGD 
Kat2bMouseesophagus squamous cell carcinoma  ISOKAT2B (Homo sapiens)mRNA:decreased expression:esophagus (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kat2b  (lysine acetyltransferase 2B)

Genes (Mus musculus)
Kat2b  (K(lysine) acetyltransferase 2B)

Genes (Homo sapiens)
KAT2B  (lysine acetyltransferase 2B)


Additional Information