Cancer-Suppressing Gene Tied to Female Fertility

By Steven Reinberg
HealthDay Reporter
Thursday, November 29, 2007; 12:00 AM

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WEDNESDAY, Nov. 28 (HealthDay News) - A gene long linked to suppressing the growth of cancer may also play a vital role in human reproduction, researchers report.

In experiments with mice, researchers found that females lacking the p53 gene had fewer embryos implanted in the uterus, less chance of becoming pregnant, and when they did conceive, they had fewer offspring. A lack of p53 did not affect the fertility of male mice, however.

"This is an amazing new function for a gene that everybody thought they knew what it did," said lead researcher Arnold J. Levine, a professor at the Institute for Advanced Study, in Princeton, N.J. "This is a gene that is not only watching over us so that we cannot get cancer, but it watches over our genome so that we can develop normally," he added.

The report appears in the Nov. 29 issue of Nature.

The p53 gene responds to a variety of stresses, such as radiation damage, in ways that allow it to protect cells against cancer, Levine explained. However, he added, "We found, quite by surprise, the normal function of p53 in the uterus of mice."

In order for embryos to implant in the uterus, a cytokine called LIF (leukemia inhibitory factor) is essential, and "p53 turns on the gene that makes LIF," Levine explained. "It's estrogen plus p53 making LIF that allows implantation."

In mice without the p53 gene, males are fine, but females only infrequently implant eggs and "the litter sizes go way down," Levine said. However, when these mice were given an injection of LIF, they reproduced normally.

Whether this finding has implications for humans isn't clear, Levine said. "We do know that humans require LIF in the uterus, but whether p53 has the same function in humans is something we are working on," he said.

Levine believes that p53 could play a part in human reproduction and infertility, but "there must be other factors as well," he said.

Defects in p53 are extremely rare in humans. "There are about 250 families in the United States that have defects in the p53 gene, a condition called Li-Fraumeni syndrome. This syndrome predisposes patients to cancer at an early age," Levine said.