Photo by Theresa Naujack
A mechanism discovered by Hutch scientists explains how a well-known gene that is implicated in numerous cancers may give tumors a growth advantage.
Tumors require extra factors for growth, which are supplied by the formation of new blood vessels, a process called angiogenesis.
Dr. Paul Neiman, an investigator in the Basic Sciences and Human Biology divisions, working with staff scientist Dr. Alanna Ruddell and technician Kim Brandvold, have found that a cancer-promoting gene called myc can enhance angiogenesis in cancer cells.
In a paper published last year in Oncogene, the group showed that myc, a gene that also plays a role in normal cell growth and proliferation, can stimulate the process of angiogenesis in chickens with lymphoma, a cancer that affects immune system cells called B cells.
Exact role unknown
Although an increase in myc expression is a common feature of many human cancers, the exact role of myc in tumorigenesis is not yet known.
The identification of myc-induced angiogenesis in chicken B cell lymphomas suggests that this function could also be occurring in human cancers showing an increase in myc expression.
Like many other cancer researchers, Neiman doesn't actually work with cancer patients or human tissues but with an accessible model organism that mirrors the properties of cancer seen in humans.
While his lab's choice of using a bird to study human cancer may seem atypical, Neiman pointed out the advantages of his system.
"The chicken is an attractive model to study both normal cell function and the various stages of cancer," said Neiman, who has studied these phenomena for almost 30 years.
Neiman's laboratory studies both tumorigenesis and normal cell development in the chicken bursa of Fabricius, an organ that is found only in birds. The bursa is a lymphoid tissue associated with the gut that is responsible for the development of B cells. B cells produce antibodies that aid in the defense against infection.
Neiman said that an understanding of the normal function of the bursa has aided studies on cancer.
"Like any other model system," he said, "the more you know about it, the more you can exploit it."
Neiman began his work with the chicken while investigating how viruses contribute to the formation of tumors.
The first retrovirus identified and shown to cause cancer, the Rous sarcoma virus, was originally isolated from chickens. Neiman's laboratory was among the first to demonstrate how retroviruses cause cancer by inserting their DNA into the DNA of the chicken cells. The virus transforms the behavior of the infected cells, allowing them to divide under circumstances in which normal cells would not. The transformed cells undergo further genetic changes leading to the formation of tumors.
Programmed cell death
The chicken bursa is composed of follicles where early stem cells divide and develop into mature B cells.
Only a small proportion of bursal B cells made actually complete maturation and leave the bursa. The majority of the cells undergo a programmed cell death called apoptosis.
"The rate of spontaneous apoptosis in the bursa is enormous," Neiman said. "Since only a small population of cells are needed for B cell maturation, apoptosis may be a way of disposing of the non-ideal cells."
Normal bursa cells are ordered in a distinct architecture within the follicle and require neighboring cell contact in order to survive.
"When bursal cells are separated in culture conditions, they undergo rapid cell death," Neiman said.
To identify genes that may be involved in regulating the apoptotic pathway, Neiman and the DNA Array Facility at the Hutch have developed a chick microarray chip that contains approximately 3,000 genes from normal and transformed follicles. The chip enables Neiman to monitor the activity of all 3,000 genes simultaneously.
Neiman's lab uses the chip to identify molecules that regulate the process of apoptosis.
Since there are no plans for sequencing the chick genome, the microarray chip is the best source for finding novel genes involved in both normal chick development and tumorigenesis.