Mar. 30, 2004 Researchers at Jefferson Medical College have uncovered a novel pattern of gene expression in the stem cell-rich bottom of tiny "crypts" in the tissue lining the colon. By identifying these patterns, the scientists hope to be able to identify mechanisms through which stem cells contribute to the development of colon cancer.
"Having a genetic signature for the colonic stem cell will give us a tool to investigate the hypothesis that stem cell overpopulation is the key to colon cancer initiation," says Bruce Boman, M.D., Ph.D., director of the Division of Genetic and Preventive Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia and Jefferson's Kimmel Cancer Center, who led the work. Dr. Boman presents his team's findings March 30 at the annual meeting of the American Association for Cancer Research in Orlando. According to Dr. Boman, a form of inherited colon cancer, familial adenomatous polyposis, or FAP, may begin when processes that regulate adult stem cells in the colon go awry. To try to understand some of these processes, Dr. Boman and his team decided to first look at the genes expressed in normal colon crypts.
The researchers examined sections of the top, middle and bottom of crypts, using microarray technology to analyze which genes are selectively expressed in each region. They were particularly interested in the genes expressed in the bottom of the crypt, where the stem cells reside.
"We've found some intriguing patterns of gene expression – patterns that suggest a unique genetic signature for stem cells," says research technician Moreh Salunek. "We were looking at genes that were unique and up-regulated in the bottom of the crypt, and found that the majority were related to binding processes and catalytic enzymes." Some were surprising, she says, such as STAMP1, a gene implicated as a marker for the progression of prostate cancer. They also found a gene called HOXD4, which is a developmental gene involved in the formation of the gut.
Stem cells in the normal colon produce daughter cells that proliferate and make their way to the crypt top, where they differentiate into specialized colon cells, says Dr. Boman. Colon cancer is marked by a change in the distribution pattern of proliferating daughter cells. Next, the researchers plan to use their novel gene profile to investigate cellular changes in colon cancer development. They also plan to use a different microarray to expand the number of genes they can examine.
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