Gene Blocking Fails to Stop Tumor Growth

Cancer researchers have found that blocking genes to prevent tumor growth is only temporarily successful, as cells that survive the treatment grow back in a manner that is often no longer regulated by the gene.

Investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA; www.med.upenn.edu) worked with a mouse model to study the effect of blocking c-MYC regulation on mammary cancer. C-Myc, a proto-oncogene located at 8q24, is a member of the Myc gene family that also includes the closely related N-Myc, L-Myc, P-Myc, R-Myc, S-Myc, and B-Myc genes. C-Myc spans 6-7 kb of genomic DNA, and codes for 439 amino acids. The C-Myc gene encodes a 66 kDa nuclear DNA-binding protein that regulates gene transcription and is responsible for growth control and cell cycle progression. The location of the C-Myc gene has been identified as one of the three most commonly amplified genomic regions in breast cancer, and C-Myc overexpression has been described in 70-100% of breast cancer tissues.

Previous research had suggested that preventing C-Myc expression would stop the growth of mammary cancers. However, results published in the December 2004 issue of Cancer Cell revealed that 50% of c-Myc-induced mammary cancers were able to grow in a mouse model lacking c-Myc expression. In addition, residual cancer cells remained from virtually all tumors that did regress, and these residual cells rapidly recovered their malignant properties following c-MYC reactivation or spontaneously recurred in a MYC-independent manner.

Senior author Dr. Lewis A. Chodosh, associate professor of cancer biology and medicine at the University of Pennsylvania School of Medicine, explained, "When physicians apply a selective pressure to a tumor by blocking an oncogenic pathway, cells escape. They find a back door and progress to a more aggressive state that becomes independent of that pathway.”




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