title: Hexachlorobenzene alters cell cycle by regulating p27-cyclin E-CDK2 and c-Src-p27 protein complexes.
abstract: 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 (0.005μM) promotes the cell cycle progression, enhances cyclin D1expression, and reduces the nuclear localization of p27 accompanied by an increased interaction between p27 and c-Src kinase. On the other hand, 5μM 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.
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Ventura
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Núñez
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: V
authors.initials: V
authors.lastname: Gaido
authors.affiliation: Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Pontillo
authors.affiliation: Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Miret
authors.affiliation: Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Randi
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; Instituto de Química y Fisicoquímica Biológicas "Prof. Alejandro C. Paladini", IQUIFIB UBA-CONICET, Buenos Aires, Argentina. Electronic address: cmcocca@ffyb.uba.ar.
authors.forename: C
authors.initials: C
authors.lastname: Cocca
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D006581:Hexachlorobenzene / Q000633:toxicity*; D006801:Humans; D061986:MCF-7 Cells; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006581:Hexachlorobenzene; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: Cell cycle; Cyclin E; Hexachlorobenzene; c-Src; p27