title: Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer.
abstract: Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (n=68) and non-kinases (n=26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis.
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors: Javier
authors: J
authors: Rivero
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors: Luis Alberto
authors: LA
authors: Henríquez-Hernández
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors: Octavio P
authors: OP
authors: Luzardo
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors: José
authors: J
authors: Pestano
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors: Manuel
authors: M
authors: Zumbado
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain.
authors: Luis D
authors: LD
authors: Boada
authors: Research Group in Environment and Health, Research Institute of Biomedical and Health Sciences (IUIBS), Universidad de Las Palmas de Gran Canaria and Instituto Canario de Investigación del Cáncer (ICIC), Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Spain. Electronic address: pilarfdez.valeron@ulpgc.es.
authors: Pilar F
authors: PF
authors: Valerón
mesh_terms: D001940:Breast / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000139:chemically induced*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D009857:Oncogenes; D011494:Protein Kinases / Q000235:genetics
chemical_list: D006843:Hydrocarbons, Chlorinated; D011494:Protein Kinases
keywords: Breast cancer; Gene expression; HMEC; Organochlorine mixtures; Xenoestrogens