Expression of nuclear receptor interacting proteins TIF-1, SUG-1, receptor interacting protein 140, and corepressor SMRT in tamoxifen-resistant breast cancer.

Abstract

Regulation of gene transcription as a consequence of steroid receptor-DNA interaction is mediated via nuclear receptor interacting proteins (RIPs), including coactivator or corepressor proteins, which interact with both the receptor and components of the basic transcriptional unit and vary between cell types. The aim of this study was to test the hypothesis that resistance of some breast carcinomas to tamoxifen was associated with inappropriate expression of some of these RIPs. Using Northern analysis, we observed no significant difference between the amount of either TIF-1 or SUG-1 mRNA expressed in parental MCF-7 and MCF-7 tamoxifen-resistant cell lines. However, the expression of RIP140 mRNA was lower in the resistant cell line and in the presence of estradiol, the level of RIP140 mRNA was higher in the resistant cells but not in the parental cells. In a cohort of 19 tamoxifen-resistant breast tumor samples, there was no significant difference in the level of the RIP140 and TIF-1 and corepressor SMRT mRNA compared with tamoxifen-treated tumors (n = 6) or untreated tumors (n = 21). However, SUG-1 mRNA was lower in resistant breast tumors. These data provide no support for increased expression of these RIPs or decreased expression of corepressor SMRT for being a mechanism for resistance of breast tumors to tamoxifen.

• Authors: C M Chan, A E Lykkesfeldt, M G Parker, M Dowsett
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 5 Issue 11 Pg. 3460-7 (Nov 1999) ISSN: 1078-0432 [Print] United States
• PMID: 10589759 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents, Hormonal
• Carrier Proteins
• Intracellular Signaling Peptides and Proteins
• LIM Domain Proteins
• NRIP1 protein, human
• Nuclear Proteins
• Nuclear Receptor Interacting Protein 1
• PSMC5 protein, human
• RNA, Messenger
• Receptors, Cytoplasmic and Nuclear
• Receptors, Estrogen
• SUG1 protein, mammalian
• Transcription Factors
• transcriptional intermediary factor 1
• Tamoxifen
• Proteasome Endopeptidase Complex
• ATPases Associated with Diverse Cellular Activities

Topics

• ATPases Associated with Diverse Cellular Activities
• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents, Hormonal (therapeutic use)
• Breast Neoplasms (genetics, pathology, surgery)
• Carrier Proteins (genetics)
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Intracellular Signaling Peptides and Proteins
• LIM Domain Proteins
• Nuclear Proteins (genetics)
• Nuclear Receptor Interacting Protein 1
• Postmenopause
• Premenopause
• Proteasome Endopeptidase Complex
• RNA, Messenger (genetics)
• Receptors, Cytoplasmic and Nuclear (metabolism)
• Receptors, Estrogen (analysis, metabolism)
• Tamoxifen (therapeutic use)
• Transcription Factors (genetics)
• Transcription, Genetic
• Tumor Cells, Cultured