Metabolism Of Protein Crucial To Lymphoma Growth Uncovered

August 31, 2007 at 7:43 PM Genetics & Stem Cells News
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Metabolism Of Protein Crucial To Lymphoma Growth Uncovered
Researchers from the University of Pennsylvania and the University of Oxford have unearthed the molecular process by which the PAX5 protein, necessary for lymphocyte development, promotes the growth of common lymphomas. They hope to use this research in the fight against cancer.

Researchers found that PAX5 stimulates the growth of cancerous tumors by spurring cell division normally observed during B cell immune response. In a sense, PAX5 "hijacks" the body's own defense system designed to multiply antibody-making B cells exposed to foreign antigens.

In lymphomas, rather than facilitate an appropriate immune response, PAX5 locks the B cell division switch in the "on" position, regardless of exposure to antigens.

This is because PAX5 increases production of several key molecules comprising B cell receptor, which drives B cell expansion. Over-expression of PAX5 in mouse B cell lymphoma cell lines increased tumor growth when these cells were transplanted into mice. Conversely, dampening the expression of PAX5 decreased cancerous growth.

These latest findings on the role of PAX5 are published in the September issue of The Journal of Clinical Investigation.

Andrei Thomas-Tikhonenko, an associate professor in the Department of Pathobiology in the School of Veterinary Medicine at Penn, has studied the PAX5 gene for five years, demonstrating that PAX5 shapes the phenotype of bone marrow-derived tumors, a study published in 2003 in the journal Blood.

"We have long believed that PAX5 was involved in B-lymphomagenesis, based on the discovery of PAX-5-specific translocations and somatic hypermutations in diffuse large B cell and other non-Hodgkin lymphomas," Thomas-Tikhonenko said. "Yet at the molecular and cellular levels, the contribution of PAX5 to neoplastic growth remained undeciphered."

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