RESUMO
Mammalian sterile 20-like kinase 1/2 (MST1/2) plays an important role in cell growth and apoptosis and functions as a tumor suppressor. Previously, we showed that MST2 overexpression activates Estrogen receptor alpha (ERα) in human breast cancer MCF-7 cells in the absence of a ligand. Here, we examined the role of MST2 in the growth of ER-positive MCF-7 cells. Cell cycle, apoptosis, and mammosphere formation assay method were implemented to detect the biological effects of MST2 ablation on the growth of MCF-7 cells in vitro. The effect of MST2-siRNA on MCF-7 cells tumor growth in vivo was studied in tumor-bearing mouse model. Kaplan-Meier plotter analysis was used to determine the effect of MST2 on overall survival in breast cancer patients. MST2 overexpression increased cell viability marginally. The ablation of MST2 using siRNA dramatically suppressed the viability of the MCF-7 cells, but not ER-negative MDA-MB-231 breast cancer cells. Furthermore, MST2 knockdown increased caspase-dependent apoptosis and led to decreased mammosphere formation. Treatment of MCF-7 tumor-bearing mice with MST2 siRNA significantly inhibited tumor growth. The tumor weight was reduced further when tamoxifen was added. Patients with ER-positive breast cancer with low MST2 expression had better overall survival than did those with high MST2 expression in Kaplan-Meier survival analyses using public datasets. Our results provide new insight into the role of MST2, a key component of the Hippo signaling pathway, in mediating breast cancer progression.
Assuntos
Receptor alfa de Estrogênio , Neoplasias Mamárias Experimentais/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Inativação Gênica , Humanos , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno , Serina-Treonina Quinase 3RESUMO
Residue concentrations of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were measured in sediment core samples from two estuary areas of central Vietnam to elucidate recent status and temporal trends of pollution based on the depth profiles. Concentrations of PCBs, PBDEs, and endosulfan compounds were generally higher than those of the remaining OCPs. Peak concentrations of OCPs were found in the sediment layers corresponding to the late 1950s to the early 1980s, implying the intensive application of these insecticides in Vietnam during such periods. Although the highest PCB concentrations were measured in sediment layers dated in the 1970s, increasing PCB residues observed in the shallower layers may be related to the strong industrialization and urbanization in Vietnam. BDE-209 exhibited increasing concentrations and proportions to total PBDEs towards shallower depths, suggesting substantial use and on-going releases of deca-BDE products in recent years.