"Stable Suppression of Tumorigenicity by Virus-Mediated RNA Interference".

Thijn R. Brummelkamp ^{1, 3}, René Bernards ^{1, 3}, and Reuven Agami ^{2, 3, @}

¹ Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
² Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
³ Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

^@ Correspondence: Reuven Agami:  +31 20 512 1977 (phone);  +31 20 512 2029 (fax);
E-mail:  r.agami@nki.nl

Most human tumors harbor multiple genetic alterations, including dominant mutant oncogenes. It is often not clear which of these oncogenes are continuously required and which, when inactivated, may inhibit
tumorigenesis. Recently, we developed a vector that mediates suppression of gene expression through RNA
interference. Here, we use a retroviral version of this vector to specifically and stably inhibit expression of only the oncogenic K-RAS^V12 allele in human tumor cells. Loss of expression of K-RAS^V12 leads to loss of
anchorage-independent growth and tumorigenicity. These results indicate that viral delivery of small interfering RNAs can be used for tumor-specific gene therapy to reverse the oncogenic phenotype of cancer cells.

1. Frenster JH, "Oncogenes as Molecular Targets within Active Chromatin".

2. Blumenthal T, Evans D, Link CD, Guffanti A, Lawson D, Thierry-Mieg J, Thierry-Mieg D, Chiu WL,
Duke K, Kiraly M, and Kim SK, "A Global Analysis of Caenorhabditis elegans Operons". Nature vol. 417, no. 6891, pp. 851-854 (June 20, 2002).

3. "Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".