Blocking single gene renders tumors less aggressive, JHU researchers find

Researchers at Johns Hopkins have identified a gene that, when repressed in tumor cells, puts a halt to cell growth and a range of processes needed for tumors to enlarge and spread. The researchers hope that this so-called "master regulator" gene may be the key to developing a new treatment for cancerous tumors resistant to current drugs.

"This master regulator is normally turned off in adult cells, but it is very active during embryonic development and in all highly aggressive tumors studied to date," says Linda Resar, an associate professor of medicine, oncology, and pediatrics at the Johns Hopkins University School of Medicine. "Our work shows for the first time that switching this gene off in aggressive cancer cells dramatically changes their appearance and behavior."

A description of the experiments appears in the May 2 issue of the journal PLOS ONE.

Resar has been investigating genes in the master regulator's family, known as high mobility group or HMG genes, for two decades. In addition to their role in cancer, these genes are essential for giving stem cells their special charactersitics. In a previous study, Resar and her team devised techniques to block the HMGA1 gene in stem cells in order to study its role in those cells. In the newly reported study, the Resar team applied the same techniques to several strains of human breast cancer cells in the laboratory and found that those with blocked HMGA1 did not grow well in the breast tissue or spread to distant sites.

"From previous work, we know that HMGA1 turns on many different genes needed during very early development, but it's normally turned off by the time we're born," says postdoctoral fellow Sandeep Shah, who led the study. "Flipping that master regulator back on seems to be necessary for a cancer to become highly aggressive, and now we've seen that flipping HMGA1 off again can reverse that aggressive behavior."