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Common Signal in Cancer, Stem Cells

KOBE, JAPAN--Embryonic stem cells develop into all the different tissues of the body at the beginning of life; cancer cells often end life. Despite working at cross-purposes, the two types of cells apparently have something in common: a newfound gene involved in regulating their proliferation. "This could show that stem cell biology and oncology interact," says Ronald McKay, a molecular biologist at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Maryland.

McKay and colleague Robert Tsai, also of NINDS, first found the gene in cultured rat stem cells. The protein built from the gene was abundant while the cells were proliferating but abruptly disappeared when the cells began to differentiate, or turn into other types of cells. The researchers dubbed the new gene nucleostemin, because the protein built by the gene appears to be almost exclusively active within the cell nucleus.

That locus of activity led to "an inspired guess," says McKay. Other proteins active in the cell nucleus regulate the activity of genes that, when mutated, lead to cancer. McKay and Tsai searched human cancer cell lines and found a human version of nucleostemin.

To see what power nucleostemin wields, the researchers looked at its effects in both rat stem cells and human cancer cells. McKay and Tsai turned off production of the gene's protein through a technique known as gene silencing, and in other cases they added extra protein to the cells. Both too little and too much nucleostemin protein hindered cell proliferation. McKay and Tsai conclude that nucleostemin is involved in regulating the proliferation of both stem cells and at least some types of cancer cells, they reported at a meeting here on 20 November and in the December issue of Genes & Development.

Shin-Ichi Nishikawa, a molecular geneticist at Kyoto University, praises the work as being "an important contribution to this field." But he warns against giving too big a role to a single gene. Different types of stem cells, he says, appear to have diverse ways of regulating proliferation and differentiation. And although the link to cancer is intriguing, Nishikawa says, "We really need more data before saying anything conclusive."