TY - JOUR
T1 - Creating oral squamous cancer cells
T2 - A cellular model of oral-esophageal carcinogenesis
AU - Goessel, Gitta
AU - Quante, Michael
AU - Hahn, William C.
AU - Karada, Hideki
AU - Heeg, Steffen
AU - Suliman, Yasir
AU - Doebele, Michaela
AU - Von Werder, Alexander
AU - Fulda, Christine
AU - Nakagawa, Hiroshi
AU - Rustgi, Anil K.
AU - Blum, Hubert E.
AU - Opitz, Oliver G.
PY - 2005/10/25
Y1 - 2005/10/25
N2 - Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently found in the corresponding human cancer would significantly enhance our understanding of tumor development. Alterations in several key intracellular regulatory pathways (the pRB, p53, and mitogenic signaling pathways and the telomere maintenance system) appear to be sufficient for the neoplastic transformation of normal human cells. Nevertheless, in vitro transformation models to date depend on viral oncogenes, most prominently the simian virus 40 early region, to induce immortalization and malignant transformation of normal human epithelial cells. Here, we demonstrate a transformation model creating oral-esophageal cancer cells by using a limited set of genetic alterations frequently observed in the corresponding human cancer. In a stepwise model, cyclin D1 overexpression and p53 inactivation led to immortalization of oral keratinocytes. Additional ectopic epithelial growth factor receptor overexpression followed by c-myc overexpression as well as consecutive reactivation of telomerase induced by epithelial growth factor receptor sufficed to transform oral epithelial cells, truly recapitulating the development of the corresponding human disease.
AB - Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently found in the corresponding human cancer would significantly enhance our understanding of tumor development. Alterations in several key intracellular regulatory pathways (the pRB, p53, and mitogenic signaling pathways and the telomere maintenance system) appear to be sufficient for the neoplastic transformation of normal human cells. Nevertheless, in vitro transformation models to date depend on viral oncogenes, most prominently the simian virus 40 early region, to induce immortalization and malignant transformation of normal human epithelial cells. Here, we demonstrate a transformation model creating oral-esophageal cancer cells by using a limited set of genetic alterations frequently observed in the corresponding human cancer. In a stepwise model, cyclin D1 overexpression and p53 inactivation led to immortalization of oral keratinocytes. Additional ectopic epithelial growth factor receptor overexpression followed by c-myc overexpression as well as consecutive reactivation of telomerase induced by epithelial growth factor receptor sufficed to transform oral epithelial cells, truly recapitulating the development of the corresponding human disease.
KW - Cyclin D1
KW - Epithelial growth factor receptor
KW - Telomerase
KW - c-myc
KW - in vitro transformation
UR - http://www.scopus.com/inward/record.url?scp=27344436091&partnerID=8YFLogxK
U2 - 10.1073/pnas.0409730102
DO - 10.1073/pnas.0409730102
M3 - Article
C2 - 16239349
AN - SCOPUS:27344436091
SN - 0027-8424
VL - 102
SP - 15599
EP - 15604
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 43
ER -
