Promoter hypermethylation of the Chfr gene in neoplastic and non-neoplastic gastric epithelia

Honda, Takao; Tamura, Gen; Waki, Takayoshi; Kawata, Satoshi; Nishizuka, Satoshi; Motoyama, Teiichi

doi:10.1038/sj.bjc.6601849

Cited by 40 publications

(20 citation statements)

References 19 publications

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“…To date, only CHFR, an ubiquitin ligase (Kang et al, 2002), has been shown to be involved in the third mitotic checkpoint (Scolnick and Halazonetis, 2000). CHFR is frequently inactivated in human cancers, mostly owing to the hypermethylation of its promoter region (Mizuno et al, 2002;Honda et al, 2004;Takahashi et al, 2004;Brandes et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress

et al. 2006

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We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons. By monitoring chromosome condensation, the exogenously expressed SIRT2 was found to block the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines with a persistence of the cyclin B/cdc2 activity in response to mitotic stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability (CIN), characteristics previously reported for the CHFR protein.We further found that histone deacetylation, but not the aberrant DNA methylation of SIRT2 5 0 untranslated region is involved in the downregulation of SIRT2. Although SIRT2 is normally exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the nucleus was observed after treatment with a nuclear export inhibitor, leptomycin B and ionizing radiation in normal human fibroblasts, suggesting that nucleo-cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results suggest that the further study of SIRT2 may thus provide new insights into the relationships among CIN, epigenetic regulation and tumorigenesis. Oncogene (2007) 26, 945-957.

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Section: Introductionmentioning

confidence: 99%

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress

et al. 2006

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“…Most notably, several groups have shown that CHFR mRNA expression is lost or decreased in primary tumors and cancer cell lines when compared with matched normal tissues and cells. The best characterized means of expression loss is promoter hypermethylation, which occurs in a subset of tumors and cell lines and the frequency of which seems to be dependent on the tissue of origin (4,5,(12)(13)(14)(15)(16)(17)(18)(19)(20). Further support that CHFR may mediate tumorigenesis is that its chromosomal location, 12q24, is a site for allelic imbalance and chromosome rearrangements in several types of cancer (21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Altered Expression of the Early Mitotic Checkpoint Protein, CHFR, in Breast Cancers: Implications for Tumor Suppression

Privette¹,

González²,

Ding

et al. 2007

Cancer Research

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“…Transduce cell lines with the retrovirus construct and select for stable clones (months [12][13][14][15][16][17].…”

Section: Task 2a: Design a Retroviral Vector That Will Have Controllementioning

confidence: 99%

“…Most notably, several groups have shown that CHFR mRNA expression is lost or decreased in primary tumors and cancer cell lines when compared to matched normal tissues and cells. The best characterized means of expression loss is promoter hypermethylation, which occurs in a subset of tumors and cell lines and the frequency of which appears to be dependent on the tissue of origin (4,5,(12)(13)(14)(15)(16)(17)(18)(19)(20). Further support that CHFR may mediate tumorigenesis is that its chromosomal location, 12q24, is a site for allelic imbalance and chromosome rearrangements in several types of cancer (21)(22)(23)(24)(25) This decrease in expression led to the acquisition of many phenotypes associated with malignant progression.…”

Section: Referencesmentioning

confidence: 99%

Decreased Expression of the Early Mitotic Gene CHFR Contributes to the Acquisition of Breast Cancer Phenotypes

Privette¹

2007

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) 01-03-20072. REPORT TYPE (From -To) Annual DATES COVERED PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERUniversity of Michigan Ann Arbor, Michigan 48109-1274 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics and progression. Here, we studied both breast cancer cell lines and primary samples from breast cancer patients to investigate CHFR as a relevant tumor suppressor in breast cancer and to associate CHFR expression with clinical and pathological variables. A large percentage of samples demonstrated negative or weak CHFR protein expression or staining. In addition, lack of CHFR detection correlated with increased tumor size in patients and was weakly associated with ER-negative primary tumors. To study the effects of low CHFR expression in vitro, we decreased CHFR gene expression in mammary epithelial cells. Notably, this resulted in the acquisition of many phenotypes associated with malignant progression including higher growth rates, increased mitotic index, enhanced cellular invasion and motility, morphological changes, and aneuploidy. Considering the association between CHFR expression and breast cancer tumor size, the in vitro data presented here, and its previously published correlation with cellular response to chemotherapeutics such as Taxol, this study provides substantial evidence to identify CHFR as an important tumor suppressor in breast cancer and possibly a biomarker for tumor response to microtubule-targeting drugs like Taxol. Western blotting was performed using whole cell lysates from a panel of unsynchronized breast cancer cells and immortalized ("normal") human mammary epithelial cells (HMECs). A custom-made polyclonal antibody against the N-term...

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Promoter hypermethylation of the Chfr gene in neoplastic and non-neoplastic gastric epithelia

Cited by 40 publications

References 19 publications

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress

Altered Expression of the Early Mitotic Checkpoint Protein, CHFR, in Breast Cancers: Implications for Tumor Suppression

Decreased Expression of the Early Mitotic Gene CHFR Contributes to the Acquisition of Breast Cancer Phenotypes

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