Cancer-Suppressing Gene Tied to Female Fertility

Cancer-Suppressing Gene Tied to Female Fertility
WEDNESDAY, Nov. 28 (HealthDay News) - A gene long linked tosuppressing the growth of cancer may also play a vital role in humanreproduction, researchers report.
In experiments with mice, researchers found that females lacking thep53 gene had fewer embryos implanted in the uterus, less chance ofbecoming 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 theyknew what it did," said lead researcher Arnold J. Levine, a professor atthe Institute for Advanced Study, in Princeton, N.J. "This is a gene thatis not only watching over us so that we cannot get cancer, but it watchesover 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 radiationdamage, in ways that allow it to protect cells against cancer, Levineexplained. However, he added, "We found, quite by surprise, the normalfunction 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 thatmakes LIF," Levine explained. "It's estrogen plus p53 making LIF thatallows implantation."
In mice without the p53 gene, males are fine, but females onlyinfrequently implant eggs and "the litter sizes go way down," Levine said.However, when these mice were given an injection of LIF, they reproducednormally.
Whether this finding has implications for humans isn't clear, Levinesaid. "We do know that humans require LIF in the uterus, but whether p53has the same function in humans is something we are working on," hesaid.
Levine believes that p53 could play a part in human reproduction andinfertility, but "there must be other factors as well," he said.
Defects in p53 are extremely rare in humans. "There are about 250families in the United States that have defects in the p53 gene, acondition called Li-Fraumeni syndrome. This syndrome predisposes patientsto cancer at an early age," Levine said.
One expert believes the finding could have clinical implications.
"Some humans show genetic variation in the amount of p53 they canproduce and how well some of these variants of p53 function," said ColinStewart, a principal investigator at the Institute of Medical Biology inSingapore and author of an accompanying editorial in the journal.
One study suggested that some women who have difficulty in gettingpregnant tend to have the less efficient form of p53, Stewart noted.
"This may be why they have problems becoming pregnant, because the lessefficient form of p53 does not make sufficient amounts of LIF that arenecessary to get the embryo to attach to the wall of the uterus," Stewartsaid.
Drugs are currently being developed that would either improve the wayp53 works or block the action of defective forms of p53, Stewart said.
"Some of these drugs may turn out to be useful in helping womenconceive by improving the function of p53 in the uterus. Others may turnout to be possible contraceptives by blocking p53's function in theuterus," he added.
More information
For more information on p53, visit the National Center for BiotechnologyInformation.