si-RNA-Mediated Silencing of ADRBK1 Gene Attenuates Breast Cancer Cell Proliferation

Abstract

Breast cancer is the most prominent cause of cancer-related deaths among women worldwide. It has been found that genetic mutations play distinct roles in the onset and progression of breast cancer. Androgenic, beta, receptor kinase 1 (ADRBK1) has been reported to possess oncogenic characteristics vital for cancer cell viability. This study was designed to investigate the effects of small interference RNA (si-RNA)-mediated ADRBK1 knockdown on breast cancer cell growth in vitro. High-expression levels of ADRBK1 were observed in all tested breast cancer cell lines (MDA-MB-231, MCF-7, T-47D, and BT-474). ADRBK1 si-RNA was delivered to breast cancer cells using lentivirus delivery system. Depletion of ADRBK1 significantly attenuated the cell viability and colony-formation ability. Flow cytometry analysis further demonstrated that ADRBK1 silencing led to MDA-MB-231 cell arrest in the G 0 /G 1 phase. Collectively, these results indicate that knockdown of ADRBK1 gene has detrimental effects on breast cancer cell growth, which may be a potential therapeutic approach for the treatment of breast cancer.

G-Protein–Coupled Receptor Kinase 2 as a Potential Modulator of the Hallmarks of Cancer

“…GRK2 upregulation leads to a reinforcement of EGF or heregulin-triggered mitogenic (ERK1/2) and survival (AKT) pathways, thereby enhancing growth potential under low-serum or normal conditions and resistance to the induction of cell death by different therapeutic agents Moreover, GRK2 upregulation markedly favors anchorage-independent growth of luminal MCF7 or MDA-MB-231 basal cancer cells and increases their competence to trigger tumor growth in vivo (Nogués et al, 2016). Conversely, decreasing GRK2 levels have the opposite effect in both luminal and basal breast cancer cells (Zhang et al, 2014;Nogués et al, 2016) and sensitize breast cancer cells to chemotherapeutic agents. Activation of the HDAC6-Pin1 axis appears to underlie the positive effects of GRK2 on oncogenic hallmarks.…”

G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub

“…Enhanced GRK2 protein in breast cells strengthens EGF or heregulin-triggered mitogenic (ERK1/2) and survival (AKT) cascades, fosters proliferation, survival and anchorage-independent growth of luminal MCF7 or MDA-MB-231 basal cancer cells, and increases tumor growth in vivo in xenograft and orthotopic mouse models [111]. On the contrary, silencing GRK2 expression has opposite effects in both luminal and basal breast cancer cells [111, 178]. The molecular mechanisms underlying such positive effects of GRK2 on oncogenic hallmarks appear to involve the modulation of the HDAC6/Pin1 axis downstream of EGFR activation.…”

Two new mixed-ligand coordination polymers based on multi-N chelating ligand inhibit YAP expression and induce caspase-mediated spinal tumor cell apoptosis

“…Twenty-four hours before transient transfection, the OPM-2 cancer cells were collected and seeded into 6-well plates at a density of 5×10 5 cells/well. When cell growth was in the logarithmic stage with the confluence reaching 70–80%, the yap -siRNA and plasmid were transfected into the OPM-2 cells using Lipofectamine TM3000 Transfection Reagent (Invitrogen, USA) according to the manufacturer's protocol (21). The negative control group was transfected with negative control siRNA and vector plasmid by the same method.…”