NRIP1

Abstract: Spatial and temporal regulation of gene expression by a number of different nuclear receptors is critical in female reproduction. In this study we investigated whether the nuclear receptor corepressor nuclear receptor interacting protein 1 (Nrip1)/RIP140, which is essential for ovulation, is also required for postovulatory events, leading to pregnancy and parturition. Expression analysis indicated that Nrip1 is present in the uterus in stromal and glandular epithelial cells, primary decidual cells, and subsequently in differentiating decidual cells at the anti-mesometrial side of the implantation site. It also indicated a temporal regulation of Nrip1 in the corpora lutea at different stages of pregnancy, with increased levels at midgestation at approximately d 9.5 postcoitum (pc). By performing both embryo and ovarian transfer experiments we demonstrate that, provided the block to ovulation is by-passed, Nrip1−/− mice are capable of establishing and maintaining pregnancies. However, although the majority ...

Abstract: Background: Despite optimal primary treatment of ovarian cancer, overall prognosis is poor due to recurrences. While steroid hormone receptors are frequently expressed, the role of estrogen receptor (ER) in ovarian carcinogenesis, response to treatment or prognosis has not been established. We analyzed the gene-expression in response to estradiol (E2) and genistein (Gen) in ovarian cancer cells. Materials and Methods: Cell lines (Br-1, UL-1; Oy-1), treated with E2 (10 nM) or Gen (5 μM), were used for gene expression profiling. RT-PCR and Western immunoblotting were used to further analyze gene expression data. Results: Twenty-four genes were differentially regulated in ovarian cancer cell lines. C3, CLU, COL6A1, DLC1, NME1, NRIP1, PTEN, RAC2, S100A2 were down-regulated with E2 in Br-1 and UL-1 cells. MK167, SERPINB5, SLC7A5, CDK1NA, LCN2, PLAU, PHB2, CTSB, EGLN2, ERBB2, HMGB1, ID2, ITGB4, TOP2A were up-regulated in Oy-1 cells with E2 and/or genistein. ERBB2 and ID2 (E2 and Gen), LCN2, PHB2 and HMGB1 (Gen) were down- regulated in Br-1 cells. ERα and ERβ were detected in all cell lines at different levels. Conclusion: Variable response of ovarian cancer cells to E2 and Gen was observed. Study of ERs including splice variants, co-regulatory molecules are necessary to understand the relevance of receptors.

Abstract: Microsatellite instability (MSI) is related to the alteration of mismatch repair (MMR) genes and plays a key role in colorectal cancer (CRC) pathogenesis. We previously reported that the transcription factor Nuclear Receptor Interacting Protein 1 (NRIP1) is involved in sporadic intestinal tumorigenesis. The aim of this study was to decipher its role in MSI CRC. By using different mouse models and engineered cell lines, we demonstrated that NRIP1 increased MSH2 and MSH6 MMR gene transcription and mRNA/protein levels. In human CRC cells, NRIP1 expression was associated with decreased MSI and the hypermutator phenotype, and with resistance to chemotherapy drugs. Using a cohort of 194 CRC patients, we detected in 22% of the cases a MSI-induced frameshift mutation in the NRIP1 coding sequence. This genetic alteration generates a truncated protein with a dominant negative activity that increased human CRC cell proliferation and impaired the regulation of MSH2 and MSH6 gene expression. Moreover, the NRIP1 mutant correlated with a decreased overall survival of patients with advanced CRC, especially when MLH1-deficient. By decreasing the expression of MSH2 and MSH6 gene expression, the NRIP1 variant may amplify MLH1-dependent CRC progression and behave as a new prognostic marker of advanced MSI CRC.