Pregnancy spurs a tumor suppressor

Women who undergo a full-term pregnancy at an early age are less likely to develop

breast cancer than are women who never get pregnant. Scientists experimenting with

rodents now have evidence that a cancer-fighting protein called p53 accounts for

this protection.

The researchers propose that estrogen and progesterone, produced in abundance

during pregnancy, alter breast cells in some fundamental way that enables them to

produce ample p53 later in life. This girds cells against substances or various

types of energy, such as radiation, that scramble DNA. These genetic

rearrangements can start the cell proliferation that marks cancer.

Other researchers have suggested that pregnancy hormones make a woman’s breasts

more resistant to cancer because they cause breast cells to differentiate into new

structures, including ducts to transport milk. This differentiation decreases the

number of certain breast cells present in so-called terminal end buds, which some

scientists suspect are susceptible to cancer.

Bert W. O’Malley and his colleagues at the Baylor College of Medicine in Houston

conducted pregnancy-simulation experiments in which they gave young female rats

and mice that hadn’t ever been pregnant injections of estrogen and progesterone

over several weeks. Other never-pregnant mice received an inert substance. The

team also studied rodents that had given birth and nursed pups but received no


When subsequently injected with cancer-causing chemicals, animals that had

received hormones or had been pregnant responded by producing more p53 protein in

breast cells than untreated animals did.

Ten days after exposure to a carcinogen, rodents that had received hormones or had

been pregnant showed markedly less cell proliferation in the breast tissues than

did animals that had received inert injections. Most of the study’s results are

slated to appear in the Oct. 23 Proceedings of the National Academy of Sciences.

Besides estrogen and progesterone, prolactin and various other hormones trigger

the differentiation of mammary tissue during pregnancy. But drugs that stimulate

prolactin failed in a past test to protect animals against carcinogens. To see

whether p53 explains the difference, O’Malley and his colleagues induced prolactin

production in some rats and then tested their cells for p53.

Breast cells in these animals showed no more p53 when exposed to carcinogens than

did cells in animals getting a placebo. That suggests that it’s the estrogen and

progesterone in the hormone mix, not the presence of prolactin and its effects,

that spur production of cancer-protective p53, say the researchers.

In other words, “differentiation doesn’t explain the protection you get from

pregnancy-hormone release,” says Geoffrey L. Greene of the University of Chicago.

The p53 molecule switches various genes on and off, and the resulting chain of

events probably brings about a form of suicide in cancer cells, which halts

progression of the disease, says Lewis A. Chodosh of the University of

Pennsylvania in Philadelphia. It may also halt the cell’s normal cycle of growth

and division. This freezing of the cell cycle would enable DNA damaged by

carcinogens to be repaired by the cell’s built-in maintenance machinery, Chodosh


The p53 protein isn’t abundant in normal tissues. This study suggests that

estrogen and progesterone released in pregnancy “activate a long-lasting p53

switch,” says D. Joseph Jerry of the University of Massachusetts in Amherst. Still

unclear is how the hormones perform this feat, says Jerry.

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