Malignant transformation of an epithelial cell by v-Src via tv-a-mediated retroviral infection: a new cell model for studying carcinogenesis.
Most human cancers are of epithelial origin, but many cell culture models for the study of cancer-causing genes use fibroblasts. In addition, efficient delivery and stable expression of foreign genes into non-transformed cell lines are often difficult. To address both questions, we here established a non-transformed rat kidney epithelial RK3E cell line that constitutively expresses tv-a (receptor for subgroup A avian leukosis virus, ALV) for delivery of foreign genes via avian retroviral infection. This cell line (RK3E/tv-a) allows efficient and stable expression of either single or multiple foreign genes. Furthermore, tv-a-mediated delivery of various oncogenes (v-src, H-ras, myc or akt) leads to malignant transformation. v-src-transformed cells exhibited classical cancerous phenotypes in vitro, and induced tumor formation and lung metastasis upon injecting into immunodeficient mice. Expression profiles of downstream molecular effectors (E-cadherin, beta-catenin, cyclin D1, Myc, VEGF, MMP-2, and MMP-9) in these cells correlate with characteristics of cancerous phenotypes. This new cell model serves as a useful tool to study cancer-causing genes in epithelial cell type.
Fu
Shu-Ling
SL
Institute of Traditional Medicine, National Yang-Ming University, 155, Sec.2, Li-Nong St., Taipei 11221, Taiwan. slfu@ym.edu.tw
Huang
Yu-Jing
YJ
Liang
Fong-Pin
FP
Huang
Yung-Fen
YF
Chuang
Ching-Feng
CF
Wang
Shih-Wei
SW
Yao
Ju-Wen
JW
D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods
D030161:Avian Proteins; D011991:Receptors, Virus; C088745:Tva receptor; D015688:Oncogene Protein pp60(v-src)