title: Pit-1 inhibits BRCA1 and sensitizes human breast tumors to cisplatin and vitamin D treatment.
abstract: The POU class 1 homeobox 1 (POU1F1, also known as Pit-1), pertaining to the Pit-Oct-Unc (POU) family of transcription factors, has been related to tumor growth and metastasis in breast. However, its role in response to breast cancer therapy is unknown. We found that Pit-1 down-regulated DNA-damage and repair genes, and specifically inhibited BRCA1 gene expression, sensitizing breast cancer cells to DNA-damage agents. Administration of 1α, 25-dihydroxy-3-epi-vitamin D3 (3-Epi, an endogenous low calcemic vitamin D metabolite) reduced Pit-1 expression, and synergized with cisplatin, thus, decreasing cell proliferation and apoptosis in vitro, and reducing tumor growth in vivo. In addition, fifteen primary cultures of human breast tumors showed significantly decreased proliferation when treated with 3-Epi+cisplatin, compared to cisplatin alone. This response positively correlated with Pit-1 levels. Our findings demonstrate that high levels of Pit-1 and reduced BRCA1 levels increase breast cancer cell susceptibility to 3-Epi+cisplatin therapy.
authors.affiliation: Department of Physiology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.|Center for Research in Molecular Medicine and Chronic Diseases-CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Samuel
authors.initials: S
authors.lastname: Seoane
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases-CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.|Department of Obstetrics and Gynecology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Efigenia
authors.initials: E
authors.lastname: Arias
authors.affiliation: Department Organic Chemistry, Research Laboratory Ignacio Rivas, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Sigueiro
authors.affiliation: Department of Physiology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.|Center for Research in Molecular Medicine and Chronic Diseases-CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sendon-Lago
authors.affiliation: Department of Physiology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.|Center for Research in Molecular Medicine and Chronic Diseases-CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Anxo
authors.initials: A
authors.lastname: Martinez-Ordoñez
authors.affiliation: Oncology and Genetics Unit, Biomedical Research Institute of Vigo (IBIV), Complejo Hospitalario Universitario de Vigo, Servicio Galego de Saude (SERGAS), Vigo 36036, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Castelao
authors.affiliation: Research Unit, Fundación Hospital de Jove, Gijón 33290, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Eiró
authors.affiliation: Department of Morphological Sciences, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Garcia-Caballero
authors.affiliation: Department of Obstetrics and Gynecology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Macia
authors.affiliation: Department of Clinical Oncology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lopez-Lopez
authors.affiliation: Department Organic Chemistry, Research Laboratory Ignacio Rivas, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Maestro
authors.affiliation: Research Unit, Fundación Hospital de Jove, Gijón 33290, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vizoso
authors.affiliation: Department Organic Chemistry, Research Laboratory Ignacio Rivas, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mouriño
authors.affiliation: Department of Physiology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.|Center for Research in Molecular Medicine and Chronic Diseases-CIMUS, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Fernandez
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D006801:Humans; D050817:Transcription Factor Pit-1 / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D050817:Transcription Factor Pit-1; D014807:Vitamin D; D002945:Cisplatin
keywords: BRCA1; Pit-1; breast cancer; cisplatin; vitamin D