Gene Blocking Fails to Stop Tumor Growth

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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