New Jackson Laboratory researcher investigates pathways that promote cell growth . . . and cancer
Date: January 30, 2007
Bar Harbor, Maine - We all have, lurking within us, genes that can give us cancer. These so-called proto-oncogenes sound ominous, but when they function properly, they orchestrate development and growth with astonishing precision. A single cell divides, differentiates and grows into a viable, functional organism. When something goes awry, however, the precision is lost, and the consequences can be severe. In adults, growth promoters and regulators can transform into mechanisms for uncontrolled cell division and growth, otherwise known as cancer.
Associate Staff Scientist Casey Fox, Ph.D., at The Jackson Laboratory, studies a family of these sometimes wayward genes called the PIM kinases. Kinases are proteins that serve to activate or de-activate other proteins, and there are about 520 known kinases in the human genome. As a group, kinases represent a large fraction of cancer-causing genes. The PIM family, PIM-1 through PIM-3, were first cloned in the early 1980s and have since been implicated in many cancers, including leukemia and prostate cancer. The ways in which the PIM kinases regulate cell growth have only recently begun to become clear.
Characterizing his work as “biochemistry for the post-genomics era,” Fox seeks to use gene sequence and other accumulated data to go back and learn much more exactly how the PIM kinases work. One intriguing trait is that they work together. Animals with one PIM kinase gene knocked out (deleted) are viable and appear quite normal. An animal that lacks all three genes is about 30% smaller with 30% fewer cells than normal throughout all systems, indicating that the PIM kinases are universal regulators of cell division and growth in all tissues.
“They’re different from other kinases. Kinases are typically cell or tissue specific, but PIM kinases are produced in every cell you’d care to look at,” said Fox. “Their function also seems to be regulated differently. Understanding how the PIM kinases work is key to unlocking their therapeutic potential in patients.”
Learning more about the root causes for cancer is just one possible application of Fox’s research. A newly discovered and exciting aspect of the PIM kinases is their potential role in the immune response. While mice that lack PIM-1 and PIM-2 have an immune system that appears to be normal, they fail to generate an immune response when challenged with infectious bacteria.
“This offers the potential to develop a way to be able to affect the immune response while keeping all the cells and systems intact,” said Fox. “That would greatly improve procedures that require the immune system to be suppressed, such as organ transplants or treatment of autoimmune diseases.”
The Jackson Laboratory, founded in 1929, is the world's largest mammalian genetics research institution, with facilities in Bar Harbor, Maine, and West Sacramento, Calif. Its research staff of more than 450 investigates the genetic basis of cancers, heart disease, osteoporosis, Alzheimer's disease, glaucoma, diabetes, and many other human diseases and disorders. The Laboratory is also the world's source for more than 3,000 strains of genetically defined mice, home of the Mouse Genome Database and many other publicly available information resources, and an international hub for scientific courses, conferences, training and education.
Contact(s): Joyce Peterson, joyce.peterson@jax.org, 207-288-6058
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