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Bmi1 combines with oncogenic KRAS to induce malignant transformation of human pancreatic duct cells in vitro.
Chen, Shao-Jie; Chen, Yin-Ting; Zeng, Lin-Juan; Zhang, Qiu-Bo; Lian, Guo-da; Li, Jia-Jia; Yang, Ke-Ge; Huang, Chu-Mei; Li, Ya-Qing; Chu, Zhong-Hua; Huang, Kai-Hong.
Afiliación
  • Chen SJ; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road No. 107, Guangzhou, 510120, People's Republic of China.
  • Chen YT; Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • Zeng LJ; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road No. 107, Guangzhou, 510120, People's Republic of China.
  • Zhang QB; Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • Lian GD; Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
  • Li JJ; Department of Gastroenterology, Lihuili Hospital of Ningbo Medical Center, Ningbo, China.
  • Yang KG; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road No. 107, Guangzhou, 510120, People's Republic of China.
  • Huang CM; Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • Li YQ; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road No. 107, Guangzhou, 510120, People's Republic of China.
  • Chu ZH; Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • Huang KH; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road No. 107, Guangzhou, 510120, People's Republic of China.
Tumour Biol ; 37(8): 11299-309, 2016 Aug.
Article en En | MEDLINE | ID: mdl-26951514
It is critical to understand the pathogenesis of preinvasive stages of pancreatic duct adenocarcinoma (PDAC) for developing novel potential diagnostic and therapeutic targets. The polycomb group family member B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi1) is overexpressed and involved in cancer progression in PDAC; however, its role in the multistep malignant transformation of human pancreatic duct cells has not been directly demonstrated. In this study, we stably expressed Bmi1 in a model of telomerase-immortalized human pancreatic duct-derived cells (HPNE) and showed that Bmi1 promoted HPNE cell proliferation, migration, and invasion but not malignant transformation. We then used mutant KRASG12D as a second oncogene to transform HPNE cells and showed that it further enhanced Bmi1-induced malignant potential. More importantly, coexpression of KRASG12D and Bmi1 caused anchorage-independent growth transformation in vitro but still failed to produce tumors in nude mice. Finally, we found that mutant KRASG12D induced HPNE-Bmi1 cells to undergo partial epithelial-mesenchymal transition (EMT) likely via upregulation of snail. Knockdown of KRASG12D significantly reduced the expression of snail and vimentin at both the messenger RNA (mRNA) and protein level and further impaired the anchorage-independent growth capability of invasive cells. In summary, our findings demonstrate that coexpression of Bmi1 and KRASG12D could lead to transformation of HPNE cells in vitro and suggest potential new targets for diagnosis and treatment of PDAC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Transformación Celular Neoplásica / Proteínas Proto-Oncogénicas p21(ras) / Carcinoma Ductal Pancreático / Complejo Represivo Polycomb 1 Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Tumour Biol Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Transformación Celular Neoplásica / Proteínas Proto-Oncogénicas p21(ras) / Carcinoma Ductal Pancreático / Complejo Represivo Polycomb 1 Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Tumour Biol Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article Pais de publicación: Países Bajos