UT Arlington biochemists say
their newly published study brings researchers a step closer to understanding
how the commonly used synthetic compound bisphenol-A, or BPA, may promote
breast cancer growth.
Subhrangsu Mandal, associate
professor of chemistry/biochemistry, and Arunoday Bhan, a PhD student in
Mandal’s lab, looked at a molecule called RNA HOTAIR. HOTAIR is an abbreviation
for long, non-coding RNA, a part of DNA in humans and other vertebrates. HOTAIR
does not produce a protein on its own but, when it is being expressed or
functioning, it can suppress genes that would normally slow tumor growth or cause
cancer cell death.
High levels of HOTAIR expression
have been linked to breast tumors, pancreatic and colorectal cancers, sarcoma
UT Arlington researchers found
that when breast cancer and mammary gland cells were exposed to BPA in lab
tests, the BPA worked together with naturally present molecules, including
estrogen, to create abnormal amounts of HOTAIR expression. Their results were
published online in February by the Journal of Steroid Biochemistry and
“We can’t immediately say BPA
causes cancer growth, but it could well contribute because it is disrupting the
genes that defend against that growth,” said Mandal, who is corresponding
author on the paper.
“Understanding the developmental
impact of these synthetic hormones is an important way to protect ourselves and
could be important for treatment,” he said.
Bhan is lead author on the new
paper. Co-authors include Mandal lab members Imran Hussain and Khairul I
Ansari, as well as Linda I. Perrotti, a UT Arlington psychology assistant
professor, and Samara A.M. Bobzean, a member of Perrotti’s lab.
“We were surprised to find that BPA
not only increased HOTAIR in tumor cells but also in normal breast tissue,”
said Bhan. He said further research is needed, but the results beg the question
– are BPA and HOTAIR involved in tumor genesis in addition to tumor growth?
BPA has been widely used in
plastics, such as food storage containers, the lining of canned goods and,
until recently, baby bottles. It belongs to a class of endocrine disrupting
chemicals, or EDCs, which have been shown to mimic natural hormones. These
endocrine disruptors interfere with hormone regulation and proper function of human
cells, glands and tissue. Previous studies have linked BPA to problems with
reproductive development, early puberty, obesity and cancers.
Under normal circumstances,
estrogen regulates HOTAIR, turning its expression on and off through
interaction with molecules called estrogen-receptors, or ERs, and estrogen
receptor-coregulators, or ER-coregulators. The new study found that BPA
disrupts the normal function of the ERs and the ER-coregulators when estrogen
was present and when it wasn’t, potentially implicating it in tumor growth in a
variety of cancers.
work is at its best when results can shed light on issues of public concern.
Dr. Mandal and his team are using their expertise to do just that. Their
findings continue to advance what we know about how the chemicals in our
environment could be affecting us in unseen ways," said Pamela
Jansma, dean of the UT Arlington College of Science.
Researchers saw similar results when they exposed HOTAIR
to a synthetic estrogen called diethylstilbestrol (DES). DES has been shown to
increase risks of breast cancer and other health problems in women who used it
and their daughters. It was formerly used as a hormone replacement and as an
attempt to prevent pregnancy complications.
The new paper is called “Bisphenol-A
and diethylstilbestrol exposure induces the expression of breast cancer
associated long noncoding RNA HOTAIR in vitro and in vivo.” It is available
The National Institutes of
Health and American Heart Association funded Mandal’s research into endocrine
The University of Texas at Arlington is a
comprehensive research institution and the second largest institution in The
University of Texas System. The Chronicle of Higher Education ranked UT
Arlington as the seventh fastest-growing public research university in 2013. U.S.
News & World Report ranks UT Arlington fifth in the nation for
undergraduate diversity. Visit www.uta.edu to learn more and follow #UTAdna.