Hexachlorobenzene alters cell cycle by regulating p27-cyclin E-CDK2 and c-Src-p27 protein complexes
| Autor: | Noelia Miret, Andrea Randi, Carolina Pontillo, Vanesa Elisabeth Gaido, Mariel Núñez, Clara Ventura, Claudia Cocca |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cyclin E CIENCIAS MÉDICAS Y DE LA SALUD Cyclin D P27 Ciencias de la Salud Toxicology CSK Tyrosine-Protein Kinase 03 medical and health sciences Cyclin-dependent kinase Internal medicine medicine Hexachlorobenzene Humans Cyclin D1 Phosphorylation Cyclin Cell Proliferation Oncogene Proteins biology Kinase Cell growth Chemistry C-Src Cyclin-dependent kinase 2 Cyclin-Dependent Kinase 2 Cell Cycle General Medicine Cell cycle Cell biology Otras Ciencias de la Salud 030104 developmental biology Endocrinology src-Family Kinases biology.protein MCF-7 Cells Cell Division Cyclin-Dependent Kinase Inhibitor p27 |
| Popis: | Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea–induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7. Here, we show that HCB alters cell cycle in a concentration-dependent way. The lowest assessed concentration (0.005 μM) promotes the cell cycle progression, enhances cyclin D1 expression, and reduces the nuclear localization of p27 accompanied by an increased interaction between p27 and c-Src kinase. On the other hand, 5 μM HCB delays the cell cycle progression and promotes the formation of the cyclin E-CDK2-p27 protein complex. Our results show that HCB stimulates cell proliferation through cell cycle modulation and c-Src involvement in MCF-7 cells. Here, we report for the first time that differential mechanisms of action of HCB on mammary cell cycle progression are triggered at different concentrations of this pollutant. Fil: Ventura, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Núñez, M.. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Gaido, Vanesa Elisabeth. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Miret, Noelia Victoria. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina |
| Databáze: | OpenAIRE |
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