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Biol. Res ; 53: 13, 2020. tab, graf
Article Dans Anglais | LILACS | ID: biblio-1100919

Résumé

BACKGROUND: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. RESULTS: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. CONCLUSIONS: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.


Sujets)
Humains , Animaux , Mâle , Adulte d'âge moyen , Antigènes glycanniques associés aux tumeurs/génétique , Indien Amérique Sud/génétique , Tumeurs de la vésicule biliaire/génétique , Liquide d'ascite/métabolisme , Cellules cancéreuses en culture , Tests de cancérogénicité , Chili , Profilage d'ADN , Protéine p53 suppresseur de tumeur/génétique , Cisplatine/pharmacologie , Souris de lignée NOD , Clones cellulaires/effets des médicaments et des substances chimiques , Clones cellulaires/métabolisme , Analyse de séquence d'ARN , Récepteur ErbB-2/génétique , Gènes erbB-2/génétique , Analyse de profil d'expression de gènes , Lignée cellulaire tumorale/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale/métabolisme , Désoxycytidine/analogues et dérivés , Désoxycytidine/pharmacologie , Cellules épithéliales/métabolisme , Kératine-19/génétique , Kératine-7/génétique , Carcinogenèse/génétique , Tumeurs de la vésicule biliaire/métabolisme , Antinéoplasiques/pharmacologie
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