Body clock gene may protect against breast cancer

A collection of genes that encode different proteins found in many of our tissues and organs, our biological clocks regulate our circadian rhythms.

These are behavioral and physiological changes that occur in response to the day and night cycle.

More and more studies are now beginning to tie circadian rhythm disruptions to a variety of disorders.

Alzheimer’s, stress migraines, and cancer are a few of the illnesses that have been linked to a disrupted body clock or to faulty genes that regulate it.

The link between cancer and circadian rhythms has increasingly become the focal point of medical research.

A recent study, for example, revealed that two genes — called Bmal1 and Per2 — produce a cancer-promoting protein when “jetlagged.” This, the researchers suggest, may explain why people who work night shifts are at higher risk of cancer.

Now, a new study — conducted at the Texas A&M University in College Station — suggests that the same Per2 gene may have a protective effect against the formation of mammary tumors.

The findings were published in the journal Development.

The role of Per2 in our body clock

The function of Per2, the authors of the new study explain, is to regulate the circadian rhythms found within each cell.

Circadian rhythms are controlled by a “master clock” located in the brain. Specifically, the brain’s hypothalamus hosts this central clock, which consists of over 20,000 neurons grouped in a structure known as the suprachiasmatic nucleus (SCN).

Lead investigator Weston Porter, a professor at the Texas A&M College of Veterinary Medicine and Biomedical Sciences, explains the function of Per2 within the larger mechanism of our body clock.

He explains, “Not only do we have a central clock [the SCN], but every one of our cells has one of these peripheral clocks and they’re in coordination with the central clock […].”

“When you wake up in the morning and see light,” adds Prof. Porter, “the light goes right into the brain and it triggers this molecular mechanism that regulates the (circadian rhythm) process.”

Per2 — which is short for Period 2 — is responsible for encoding the “negative feedback” in this daily cycle, explain the researchers.

Prof. Porter goes on to explain, “The negative and positive feedback mechanisms are constantly in balance, going up and down. One’s up during the day, the other one’s up at night — they oscillate right at 24 hours — but when you see light, that resets it in the morning.”

“When Per2 comes back, it suppresses another gene called BMAL or CLOCK,” he adds.

Per2 may keep breast cancer at bay

Using a transplantation mouse model, Prof. Porter and colleagues determined an additional role of Per2 besides the timekeeping one. Suppressing Per2 in mice led to abnormally developed mammary glands in the rodents.

As Prof. Porter goes on to say, “We discovered that these glands have what we call a kind of a bipotent phenotype; they’re actually halfway to cancer. [They] already have many of the characteristics you would see in a premalignant cell.”

The gene, therefore, plays a key role in the differentiation and development of mammary gland cells. Also, most of the mammary tumors have a low Per2 expression — which, the scientists explain, suggests that the body clock gene may protect against breast cancer.

“Per2 is functioning as a tumor suppressor gene associated with cell identity,” says Prof. Porter. The lead investigator also shares some of his upcoming research.

“Right now, we are investigating how our findings relate to humans,” he says. “There are studies out there showing a relationship between decreased levels of Per2 and certain types of breast cancer, which are more invasive. So, we believe that there is a direct relationship.”

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