Researchers at the UC San Diego School of Medicine have pinpointed a mechanism that may help explain how chromosomal translocations - the supposedly random shuffling of large chunks of DNA that frequently lead to cancer - aren't so random after all. They have developed a model of such chromosomal mix-ups in prostate cancer which indicates that the male sex hormone (androgen) receptor unexpectedly plays a key role in driving specific translocations in the development of cancer.
A better understanding of the origin and behavior of such translocations may ultimately lead to ways to both predict and perhaps interfere with their formation, and in turn, cancer development.
Chunru (Ruth) Lin, Liuqing (Luke) Yang and Michael G. Rosenfeld, MD, Howard Hughes Medical Institute investigator and Professor of Medicine at the UC San Diego School of Medicine, headed the basic research study, to be published on line December 3, 2009 in advance of publication in the journal Cell.
A series of studies showed that, under certain conditions involving some sort of genetic "stress" - such as cigarette smoke, a toxic chemical exposure or radiation - the androgen receptor can act in concert with several key enzymes and pathways induced by genotoxic stress to unexpectedly direct specific translocations leading to cancer.
"In the future, one goal would be to find tumor-causing translocations in breast and other cancers and develop a chemical library screen to find compounds that might inhibit these events in cancer formation/behavior," said Rosenfeld.
According to Rosenfeld, chromosome mix-ups are a hallmark of leukemias and lymphomas and, increasingly, other cancers such as more aggressive forms of prostate cancer. Scientists have known that various types of genetic stress can lead to random breaks in DNA and rearrangements in chromosomes, resulting in excessive cell growth and cancer, but the exact mechanisms have been poorly understood.