Suppressing NRIP1 inhibits growth of breast cancer cells in vitro and in vivo

Abstract

Earlier age at menarche is a major risk factor for breast cancer. Our previous study identified Nrip1 (also known as Rip140) as a candidate gene for delaying female sexual maturation (FSM) and found that knocking out Nrip1 could significantly delay FSM in mice. To investigate the effects of NRIP1 in breast cancer we used human cell lines and tissue arrays along with an in vivo study of DMBA-induced carcinogenesis in Nrip1 knockout mice. Analysis of tissue arrays found that NRIP1 is elevated in tumors compared to cancer adjacent normal tissue. Interestingly, in benign tumors NRIP1 levels are higher in the cytosol of stromal cells, but NRIP1 levels are higher in the nuclei of epithelial cells in malignancies. We also found overexpression of NRIP1 in breast cancer cell lines, and that suppression of NRIP1 by siRNA in these cells significantly induced apoptosis and inhibited cell growth. Furthermore, in vivo data suggests that NRIP1 is upregulated in DMBA-induced breast cancer. Importantly, we found that DMBA-induced carcinogenesis is suppressed in Nrip1 knockdown mice. These findings suggest that NRIP1 plays a critical role in promoting the progression and development of breast cancer and that it may be a potential therapeutic target for the new breast cancer treatments.

Downregulation of RIP140 in triple‑negative breast cancer inhibits the growth and proliferation of cancer cells

“…Lapierre et al (17) revealed that expression of RIP140 in colon carcinoma was low, and that overexpression of RIP140 in colon cancer cells promoted the expression of adenomatous polyposis coli, which inhibited the growth and metastasis of colon cancer by inhibiting the Wnt/APC/β-catenin signaling pathway. However, Aziz et al (8) demonstrated that RIP140 was highly expressed in breast cancer tissues, and that inhibition of RIP140 expression in breast cancer cells inhibited growth, proliferation and invasion in vivo and in vitro.…”

“…RIP140 also affects tumorigenesis and tumor metastasis via E2F transcription factor and Wnt/adenomatous polyposis coli (APC)/β-catenin signaling pathways (5,7). Aziz et al (8) demonstrated that inhibition of RIP140 inhibited the growth of breast cancer cells in vivo and in vitro. However, to the best of our knowledge, no previous research has investigated the association between the expression of RIP140 in TNBC and the postoperative prognosis of patients with TNBC.…”

Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

“…Th e changes in these genes expression in cells without IRE1 signaling enzyme function possible contribute in the suppression of glioma cell proliferation and tumor growth, because there are data indicating that the estrogen receptor related factors play an important role in the control of cell proliferation and apoptosis (Cho et al 2010;Lapierre et al 2015;Tiwari et al 2015). It is possible that increased expression of FAM162A, PGRMC2, TRIM16 and SLC39A6 genes as well as decreased expression of ESRRA, and NRIP1 genes (Figure 1) may contribute to the suppression of the proliferation and glioma growth from glioma cells with IRE1 knockdown (Auf et al 2010(Auf et al , 2013Aziz et al 2015;Casaburi et al 2015;Minchenko et al 2015;Zhang et al 2015;Matsushima et al 2016). Th erefore, suppressing of NRIP1, which modulates transcriptional activity of the estrogen receptor, as well as knockdown of a site-specifi c transcription regulator ESRRA/NR3B1 inhibits growth of the cancer cells in vitro and in vivo (Aziz et al 2015;Matsushima et al 2016).…”

“…It is possible that increased expression of FAM162A, PGRMC2, TRIM16 and SLC39A6 genes as well as decreased expression of ESRRA, and NRIP1 genes (Figure 1) may contribute to the suppression of the proliferation and glioma growth from glioma cells with IRE1 knockdown (Auf et al 2010(Auf et al , 2013Aziz et al 2015;Casaburi et al 2015;Minchenko et al 2015;Zhang et al 2015;Matsushima et al 2016). Th erefore, suppressing of NRIP1, which modulates transcriptional activity of the estrogen receptor, as well as knockdown of a site-specifi c transcription regulator ESRRA/NR3B1 inhibits growth of the cancer cells in vitro and in vivo (Aziz et al 2015;Matsushima et al 2016).…”

“…NRIP1 is a positive regulator of the circadian clock genes expression and involved in the regulation of various oncogenic signaling pathways, participates in the development and progression of solid tumors (Lapierre et al 2015). Recently, it was shown that suppressing of NRIP1 inhibits growth of breast cancer cells in vitro and in vivo (Aziz et al 2015). Recently, the mutations in this estrogen receptor cofactor gene were identifi ed in 12% of patients with primary endometrial cancers (Gibson et al 2016).…”