Texas A&M Study Links Breast Cancer, Body's Internal Clock
Posted May 07, 2018
For years, doctors have associated the BRCA1 and BRCA2 gene
mutations with an increased risk of breast cancer.
But researchers at Texas A&M University have now identified
another gene that may have an impact on breast cancer—associated
with the body’s circadian rhythm.
Texas A&M College of Veterinary Medicine & Biomedical
Sciences (CVM) professor Weston Porter and his team have found that
Period 2 (Per2), a regulatory mechanism within each cell’s
peripheral clock, plays a crucial function in mammalian mammary
gland development and that when suppressed, Per2 leads to severely
disrupted gland development in mice.
The findings, published in the scientific journal Development,
add to a growing list that ties disruptions to our circadian
rhythm—that is, the “central clock” mechanism in our brains—to a
higher risk of cancer progression, obesity, some neuromuscular
diseases, and other impairments, including jetlag.
Circadian rhythm is controlled by the suprachiasmatic nucleus
(SCN) in the brain’s anterior hypothalamus. In addition to
coordinating our sleep patterns, the SCN coordinates the other
peripheral clocks in our body, which run on a 24-hour cycle that
corresponds with each day.
“Not only do we have a central clock, but every one of our cells
has one of these peripheral clocks and they're in coordination with
the central clock,” Porter said. “When you wake up in the morning
and see light, the light goes right into the brain and it triggers
this molecular mechanism that regulates the (circadian rhythm)
In their study, Porter’s team evaluated Per2, which
provides the “negative feedback,” or counterbalance, to the
circadian rhythm process.
“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,” Porter said. “When
Per2 comes back, it suppresses another gene called BMAL or
Their finding—that Per2 has a crucial function outside
of timekeeping in mammalian mammary gland development where
Per2 plays a role in cell differentiation and
identity—describes a potentially important role for Per2
in breast cancer. Per2 expression is lost in a large
percentage of mammary tumors, which suggests it may have protective
“We discovered that these glands have what we call a kind of a
bipotent phenotype; they're actually halfway to cancer,” Porter
said. “They've already have many of the characteristics you would
see in a premalignant cell.
“We started to look at the mechanism associated with that and
found that the stem cell markers associated with a loss of
Per2 are more basal, which is characteristic of more
invasive cancer,” he said. “This reinforces the idea that
Per2 is functioning as a tumor suppressor gene associated
with cell identity.”
In addition to disruption of the developing mammary gland,
Porter also saw the same defect in transplant studies, showing that
it is Per2, and not just the central clock itself, that is
responsible for the lack of mammary ductal growth in the developing
Their next step is to revisit studies that correlate working a
night shift with an increased risk of breast cancer.
“Right now, we are investigating how our findings relate to
humans,” Porter said. “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.”
Understanding circadian rhythm and its effects on the body have
become increasingly important to the science community. The 2017
Nobel Prize for Physiology or Medicine was awarded to researchers
for discoveries of the molecular mechanisms controlling the
circadian rhythm, and the National Cancer Institute recently named
the role of circadian rhythms in cancer as one of their 12
provocative questions for the year.
For more information about the Texas
A&M College of Veterinary Medicine & Biomedical Sciences,
please visit our website at vetmed.tamu.edu or join us on Facebook, Instagram, and Twitter.
Contact Information: Megan Palsa, Executive Director of
Communications, Media & Public Relations, Texas A&M College
of Veterinary Medicine & Biomedical Science; firstname.lastname@example.org;
979-862-4216; 979-421-3121 (cell)
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