Inactivation of the Cdk4 Gene Halts Tumor Growth

Researchers studying the genetic basis for cancer development have found that expression of a gene called Cdk4 is essential for Ras-induced cancer development, regardless of the status of the p53 tumor suppressor gene or the presence of another frequently mutated tumor-suppressor gene, Ink4a/Arf. Their findings were published in the November 15, 2002, issue of Genes and Development.

Investigators from the University of Illinois College of Medicine (Chicago, USA; www.uic.edu) genetically engineered mouse cells to lack Cdk4 in order to determine its role in tumorigenesis. They found that while Cdk4-deficient cells grew and divided normally under standard conditions, once the Ras oncogene was activated, these cells retreated into a state of senescence that was not tumorigenic. Ras-expressing Cdk4-deficient cells also entered senescence when either the p53 or Ink4a/Arf tumor suppressor gene was inactivated. These findings indicated that Cdk4 was required for tumorigenesis even when commonly mutated tumor suppressor genes were nonfunctional.

"We found that if you knock out a single gene called Cdk4, you can still make cells cancer resistant, even if their tumor-suppressor defense mechanism is deficient,” explained senior author Dr. Hiroaki Kiyokawa, assistant professor of molecular genetics at the University of Illinois College of Medicine. "Cells still go into senescence.”

Since about 30% of human tumors display an activated Ras oncogene, the deliberate suppression of Cdk4 activity may provide an alternate stratagem for regulation of the cell growth cycle and prevention of tumorigenesis.



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