title: Establishment and characterization of xenografts and cancer cell cultures derived from BRCA1 -/- epithelial ovarian cancers.
abstract: The BRCA1 gene is responsible for a high number of hereditary breast and ovarian cancers that cluster in families with a strong genetic predisposition. Despite intense investigation, the accumulating findings on BRCA1 biological functions have not yet been translated into specific therapeutic approaches, also due to the lack of suitable experimental models. The purpose of this study was to establish and characterize cell cultures and xenografts from patients with BRCA1 -/- ovarian cancers. We derived two ovarian cancer cell lines, termed PD-OVCA1 and PD-OVCA2, both from patients previously treated with chemotherapy, that propagate in SCID mice as well as in vitro for a limited number of passages. Both cell lines expressed cytokeratins and the CA125 tumour marker. A detailed molecular characterization highlighted both constitutive and somatic genetic events that abrogate BRCA1 gene function. Both cell lines were shown to lose the wild type BRCA1 allele; intriguingly, these deletions were apparently accompanied by gain of one or more copies of the mutant alleles. Finally, a genomic profile of major chromosomal aberrations was obtained by the Multiplex Ligation-dependent Probe Amplification (MLPA) technique, which disclosed chromosomal imbalances targeting specific genes in each cell line. The PD-OVCA1 and PD-OVCA2 ovarian cancer cell lines will provide a valuable tool for new experimental models for the study of BRCA1-associated tumour biology.
authors.affiliation: Istituto Oncologico Veneto, Padova, Italy. stefano.indraccolo@unipd.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Veronica
authors.initials: V
authors.lastname: Tisato
authors.forename: Simona
authors.initials: S
authors.lastname: Agata
authors.forename: Lidia
authors.initials: L
authors.lastname: Moserle
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferrari
authors.forename: Monia
authors.initials: M
authors.lastname: Callegaro
authors.forename: Luca
authors.initials: L
authors.lastname: Persano
authors.forename: Maurizia Dalla
authors.initials: MD
authors.lastname: Palma
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Scaini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
authors.forename: Ornella
authors.initials: O
authors.lastname: Nicoletto
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Luigi
authors.initials: L
authors.lastname: Chieco-Bianchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
authors.forename: Emma
authors.initials: E
authors.lastname: D'Andrea
authors.forename: Marco
authors.initials: M
authors.lastname: Montagna
mesh_terms: D000368:Aged; D000818:Animals; D018394:CA-125 Antigen / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D005260:Female; D019398:Genes, BRCA1; D016678:Genome; D005838:Genotype; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous / Q000379:methods; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology*
chemical_list: D018394:CA-125 Antigen