تفاصيل الوثيقة

نوع الوثيقة : مقال في مجلة دورية 
عنوان الوثيقة :
Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations
Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations
 
لغة الوثيقة : الانجليزية 
المستخلص : We used CDK4/hTERT-immortalized normal human bronchial epithelial cells (HBEC) from several individuals to study lung cancer pathogenesis by introducing combinations of common lung cancer oncogenic changes (p53, KRAS, and MYC) and followed the stepwise transformation of HBECs to full malignancy. This model showed that: (i) the combination of five genetic alterations (CDK4, hTERT, sh-p53, KRAS(V12), and c-MYC) is sufficient for full tumorigenic conversion of HBECs; (ii) genetically identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation; (iii) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; (iv) high levels of KRAS(V12) are required for full malignant transformation of HBECs, however, prior loss of p53 function is required to prevent oncogene-induced senescence; (v) overexpression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRAS(V12); (vi) growth of parental HBECs in serum-containing medium induces differentiation, whereas growth of oncogenically manipulated HBECs in serum increases in vivo tumorigenicity, decreases tumor latency, produces more undifferentiated tumors, and induces epithelial-to-mesenchymal transition (EMT); (vii) oncogenic transformation of HBECs leads to increased sensitivity to standard chemotherapy doublets; (viii) an mRNA signature derived by comparing tumorigenic versus nontumorigenic clones was predictive of outcome in patients with lung cancer. Collectively, our findings show that this HBEC model system can be used to study the effect of oncogenic mutations, their expression levels, and serum-derived environmental effects in malignant transformation, while also providing clinically translatable applications such as development of prognostic signatures and drug response phenotypes. 
ردمد : 1541-7786 
اسم الدورية : Molecular Cancer Research 
المجلد : 11 
العدد : 6 
سنة النشر : 1434 هـ
2013 م 
نوع المقالة : مقالة علمية 
تاريخ الاضافة على الموقع : Wednesday, March 9, 2016 

الباحثون

اسم الباحث (عربي)اسم الباحث (انجليزي)نوع الباحثالمرتبة العلميةالبريد الالكتروني
Mitsuo SatoSato, Mitsuo باحث رئيسي  
Jill E LarsenLarsen, Jill E باحث مشارك  
Woochang LeeLee, Woochang باحث مشارك  
Han SunSun, Han باحث مشارك  
David S ShamesShames, David S باحث مشارك  
Maithili P DalviDalvi, Maithili P باحث مشارك  
Ruben D RamirezRamirez, Ruben D باحث مشارك  
Hao TangTang, Hao باحث مشارك  
John Michael DiMaioDiMaio, John Michael باحث مشارك  
Boning GaoGao, Boning باحث مشارك  

الملفات

اسم الملفالنوعالوصف
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