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Jeff Sutherland

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Cancer: A Programming Problem – Centrosomes

Photo by Thea Goepfert

Divining the Centrosome’s Role in Cancer:

Pulled from the biomedical dustbin, a peripheral organelle finds center stage

Eugene Russo, The Scientist 18:19:18, 11 Oct 2004

MUTAGENS AND MITOSIS: Section cut through the mammary gland of a rat that had been treated with the carcinogen MNU. Centrosomes (green) are arranged at the base of each nucleus (red), and 45% of cells show amplified chromosomes.

Comments from journal article reviewers often surprise or frustrate. But the reviewer response that cell biologist William Brinkley received six years ago left him stunned.

Brinkley and his collaborator, Subrata Sen at the University of Texas M.D. Anderson Cancer Center, were looking to demonstrate that a protein found on centrosomes, the organizing centers for microtubules during mitosis, disrupted cell division and possibly triggered carcinogenesis. Reviewers praised the work, but declared it incomplete. Brinkley and his colleagues, they instructed, needed to experimentally demonstrate that the protein of interest, when inserted into a diploid cell and induced to produce in excess, actually generated more centrosomes and converted the cell to aneuploidy. Amazingly, the reviewer had unwittingly asked Brinkley to prove a theory first proposed by pioneering biologist Theodor Boveri 80 years earlier.

“It was just almost uncanny,” says Brinkley, dean of the graduate school of biomedical sciences at Baylor College of Medicine, and a long-time admirer of Boveri’s work.

Boveri had a rather simple model for carcinogenesis. What distinguishes cancer cells from normal cells, he wrote in 1914, is abnormal chromosome number (later called aneuploidy); the wrong combination of chromosomes stems from aberrant centrosome number. “All he had at his disposal, literally, was a microscope,” says Jeffrey Salisbury, a professor of molecular biology at the Mayo Clinic College of Medicine in Rochester, Minn. “This guy just sat down and looked.” Following Brinkley’s lead, several researchers have rediscovered Boveri’s work in recent years while elucidating centrosome-associated cell-cycle proteins with potentially key roles in carcinogenesis.