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PMID:20074560

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Citation

Koyama, S, Wada-Hiraike, O, Nakagawa, S, Tanikawa, M, Hiraike, H, Miyamoto, Y, Sone, K, Oda, K, Fukuhara, H, Nakagawa, K, Kato, S, Yano, T and Taketani, Y (2010) Repression of estrogen receptor beta function by putative tumor suppressor DBC1. Biochem. Biophys. Res. Commun. 392:357-62

Abstract

It has been well established that estrogen is involved in the pathophysiology of breast cancer. Estrogen receptor (ER) alpha appears to promote the proliferation of cancer tissues, while ERbeta can protect against the mitogenic effect of estrogen in breast tissue. The expression status of ERalpha and ERbeta may greatly influence on the development, treatment, and prognosis of breast cancer. Previous studies have indicated that the deleted in breast cancer 1 (DBC1/KIAA1967) gene product has roles in regulating functions of nuclear receptors. The gene encoding DBC1 is a candidate for tumor suppressor identified by genetic search for breast cancer. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of the endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. In addition, DBC1 modulates ERalpha expression and promotes breast cancer cell survival by binding to ERalpha. Here we report an ERbeta-specific repressive function of DBC1. Immunoprecipitation and immunofluorescence studies show that ERbeta and DBC1 interact in a ligand-independent manner similar to ERalpha. In vitro pull-down assays revealed a direct interaction between DBC1 amino-terminus and activation function-1/2 domain of ERbeta. Although DBC1 shows no influence on the ligand-dependent transcriptional activation function of ERalpha, the expression of DBC1 negatively regulates the ligand-dependent transcriptional activation function of ERbetain vivo, and RNA interference-mediated depletion of DBC1 stimulates the transactivation function of ERbeta. These results implicate the principal role of DBC1 in regulating ERbeta-dependent gene expressions.

Links

PubMed Online version:10.1016/j.bbrc.2010.01.025

Keywords

Breast Neoplasms/genetics; Estrogen Receptor beta/antagonists & inhibitors; Estrogen Receptor beta/metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Transcription, Genetic; Transcriptional Activation; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ESR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8N163

F

Seeded From UniProt

complete

HUMAN:ESR1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCAR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92731

F

Seeded From UniProt

complete

HUMAN:CCAR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P03372

F

Seeded From UniProt

complete

HUMAN:CCAR2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCAR2

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ESR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8N163

F

Seeded From UniProt

complete

HUMAN:ESR2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SIRT1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ESR2

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ESR2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ESR1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ESR1

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SIR1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:K1967

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:K1967

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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