The inactivation of a DNA repair gene called Hus1 kills healthy cells lacking p53, according to scientists at the Cornell University College of Veterinary Medicine. Since p53 is mutated in most cancers, the team believes that inactivated Hus1 could eliminate the ability of cancerous cells with the p53 mutation to repair themselves. The study appeared November 9 in the Proceedings of the National Academy of Sciences.
Using a mouse model, the researchers explored how cells respond when both genes are inhibited. When they inactivated the Hus1 gene in healthy mammary gland tissues, it caused genome damage and cell death. When the group studied the effects of Hus1 inactivation in p53-deficient cells, which are highly resistant to cell death, they discovered that the ability of Hus1 inactivation to kill cells was even greater.
“The mutations that allow cancer cells to divide uncontrollably also make the cancer cells more dependent on certain cellular processes,” notes senior author, Robert Weiss, associate professor of molecular genetics. “We were able to exploit one such dependency of p53-deficient cells and could efficiently kill these cells by inhibiting Hus1.
“We've proven the power of inhibiting both pathways in normal tissue,” says Weiss. “Now we want to extend our knowledge to cancerous tissue and determine if the loss of Hus1 will impact the ability of cancers with p53 mutations to take hold and grow.”