Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics

Catteau, Aurélie; Harris, William H.; Xu, Chun‐Fang; Solomon, Ellen

doi:10.1038/sj.onc.1202509

Cited by 306 publications

(193 citation statements)

References 29 publications

Supporting

Mentioning

183

Contrasting

Order By: Relevance

“…A growing number of studies have linked the decreased expression of the BRCA1 gene to both the initiation and progression of sporadic breast cancer (Thompson et Jarvis et al, 1998;Ozcelik et al, 1998;Catteau et al, 1999). Characterizing the elements regulating the BRCA1 promoter is a crucial part of understanding how this change in expression occurs at the molecular level.…”

Section: Discussionmentioning

confidence: 99%

“…A series of papers has also suggested that methylation of the BRCA1 promoter may be a signi®cant factor in decreasing BRCA1 expression in sporadic breast tumors, possibly through inactivation of a CREB site (Mancini et al, 1998). However, methylation can account for decreased BRCA1 expression only in a subset of sporadic breast cancer samples (Magdinier et al, 1998;Dobrovic and Simpfendorfer, 1997;Rice et al, 1998;Mancini et al, 1998;Catteau et al, 1999). Overall, these results suggest that sporadic breast cancer may result from defects in the genes regulating the BRCA1 promoter, or that transformation leads to a concomitant down regulation of BRCA1 expression.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

GA-binding protein α/β is a critical regulator of the BRCA1 promoter

et al. 2000

View full text Add to dashboard Cite

Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced e ect in T47D cells. The main transcription factor interacting with this site was identi®ed as GABPa/b, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPa and b1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPa/b is a critical activator of BRCA1 expression, and that its activity may di er in human breast cell lines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GA-binding protein α/β is a critical regulator of the BRCA1 promoter

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In addition to inherited mutations, other means of regulating BRCA1 function may be important in sporadic tumors. The gene is down-regulated at the transcriptional level in sporadic cancer (Catteau et al, 1999;Mancini et al, 1998;Wilson et al, 1999) and the BRCA1 protein becomes mislocalized following infection with certain transforming viruses (Maul et al, 1998). There are currently no models which allow testing for the consequences of individual mutations in the human BRCA1 gene in an intact animal system.…”

Section: Discussionmentioning

confidence: 99%

Gene replacement with the human BRCA1 locus: tissue specific expression and rescue of embryonic lethality in mice

Lane¹,

Lin²,

Brown

et al. 2000

Oncogene

Self Cite

View full text Add to dashboard Cite

We have generated transgenic mice that harbor a 140 kb genomic fragment of the human BRCA1 locus (TgN´BRCA1 GEN ). We ®nd that the transgene directs appropriate expression of human BRCA1 transcripts in multiple mouse tissues, and that human BRCA1 protein is expressed and stabilized following exposure to DNA damage. Such mice are completely normal, with no overt signs of BRCA1 toxicity commonly observed when BRCA1 is expressed from heterologous promoters. Most importantly, however, the transgene rescues the otherwise lethal phenotype associated with the targeted hypomorphic allele (Brca1 DexllSA ). Brca1 7/7 ; TgN´BRCA1 GEN bigenic animals develop normally and can be maintained as a distinct line. These results show that a 140 kb fragment of chromosome 17 contains all elements necessary for the correct expression, localization, and function of the BRCA1 protein. Further, the model provides evidence that function and regulation of the human BRCA1 gene can be studied and manipulated in a genetically tractable mammalian system. Oncogene (2000) 19, 4085 ± 4090.

show abstract

“…This kind of sequence is not randomly distributed, but concentrated to GC-enriched islands (CpG islands), which usually situates at the position in or near transcription regulatory region. Sensitivity of methylation on all CpG is not the same, and the methylation level at the site of CpG can be changed [10][11][12] . Prevalent hypomethylation and local hyper methylation exist in genome of cancer tissue, for example, hypermethylation on promoters of p16, E-cadherin, and genes encoding hormone receptors and genes of DNA repair, and genes inhibiting the genesis of blood vessels may induce the absent or low expression of these gene and improve the oncogenesis and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Metastatic suppressor genes inactivated by aberrant methylation in gastric cancer

Wang

Dai²

2007

WJG

View full text Add to dashboard Cite

AIM:To screen out the differentially methylated DNA sequences between gastric primary tumor and metastatic lymph nodes, test the methylation difference of gene PTPRG between primary gastric tumor and metastatic lymph nodes, and test the regulatory function of 5-aza-2-deoxycytidine which is an agent with suppression on methylation and the level of methylation in gastric cancer cell line. METHODS:Methylated DNA sequences in genome were enriched with methylated CpG islands amplification (MCA) to undergo representational difference analysis (RDA), with MCA production of metastatic lymph nodes as tester and that of primary tumor as driver. The obtained differentially methylated fragments were cloned and sequenced to acquire the base sequence, which was analyzed with bioinformatics. With methylation-specific PCR (MSP) and RT-PCR, methylation difference of gene PTPRG was detected between primary tumor and metastatic lymph nodes in 36 cases of gastric cancer.Methylation of gene PTPRG and its regulated expression were observed in gastric cancer cell line before and after being treated with methylation-suppressive agent. RESULTS:Nineteen differentially methylated sequences were obtained and located at 5' end, exons, introns and 3' end, in which KL59 was observed to be located at 9p21 as the first exon of gene p16 and KL22 to be located at promoter region of PRPRG . KL22, as the probes, was hybridized with driver, tester and 3-round RDA products respectively with all positive signals except with the driver. Significant difference was observed in both methylation rate of gene PTPRG and PTPRG mRNA expression rate between primary tumor and metastatic lymph nodes. Demethylation of gene PTPRG , with recovered expression of PTPRG mRNA, was observed after gastric cancer cell line being treated with methylation-suppressive agent. CONCLUSION:Difference exists in DNA methylation between primary tumor and metastatic lymph nodes of gastric cancer, with MCA-RDA as one of the good analytical methods. Significant difference exists in methylation of gene PTPRG between primary tumor and metastatic lymph nodes of gastric cancer. Methylation level in gastric cancer cell line can be decreased by 5-aza-2'-deoxycytidine, which is the methylationsuppressive agent, with PTPRG expression being recovered.

show abstract

Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics

Cited by 306 publications

References 29 publications

GA-binding protein α/β is a critical regulator of the BRCA1 promoter

GA-binding protein α/β is a critical regulator of the BRCA1 promoter

Gene replacement with the human BRCA1 locus: tissue specific expression and rescue of embryonic lethality in mice

Metastatic suppressor genes inactivated by aberrant methylation in gastric cancer

Contact Info

Product

Resources

About