Contact: Andy Smith; [email protected]
Gene Linked to Breast Cancer & Male Infertility
PHILADELPHIA -- Researchers at Temple University School of
Medicine's Fels Institute for Cancer Research have discovered a gene
which is linked to excessive cell duplication in the breast, one of the
primary genetic events that occurs in breast cancers.
The researchers theorize that blocking the production of this
gene, called A-MYB (pronounce: a-mib), may be an important therapeutic approach for the treatment of breast cancer.
In addition, the researchers have discovered that under-production of this gene in males seems to be the cause of a certain type of male infertility. The findings are reported in the April 17 issue of Nature.
Breast Cancer
The experiments described in this week's issue of Nature used two
sets of male and female mice in which the A-MYB gene was eliminated using
"gene knock-out technology." This technology allowed the creation of a
new mouse species that cannot produce the A-MYB protein.
"In studying the female mice, A-MYB was found to have effects
focused on reproductive organs, primarily the breasts," says Prem Reddy,
Ph.D., chairman of the Fels Institute and lead author of the paper. "One
of the highlights of this work is the finding that over-production of the
A-MYB gene is often involved in the genesis of breast cancer."
In mammals, the breast tissue contains a set of glands called the
mammary glands. During growth and puberty, these glands continually grow
into a series of capillaries which spread throughout the breast. During
pregnancy, these capillaries divide and branch out on a massive scale
forming structures called Alveoli, which act as factories of milk
production. Fels researchers found that A-MYB is directly linked to
proliferation of breast cells, especially following pregnancy.
In the mice deprived of the A-MYB gene, it was found that these
capillaries never grew well, and would not produce milk after the
delivery of pups. Fels researchers noted that the A-MYB gene was a
growth accelerating gene in the female breast, and breast cells deprived
of the gene seemed to be incapable of growth beyond the point of
puberty.
This provided an important clue to the investigators that this
gene may play a critical role in the proliferation of breast cancer cells
as well. Their work, which will soon appear in the international cancer
journal Oncogene, shows that breast tumor cells over-produce this gene
product and require this protein for their proliferative function,
providing an important link between breast cancer and the A-MYB gene.
Their work establishes that A-MYB is the cause of the rapid division of
cells and that blocking the production of this protein is an important
therapeutic approach for the treatment of breast cancer.
Male Infertility
The role of the A-MYB protein in human health does not end with
breast development. Fels researchers also found that A-MYB plays an
important role in determining male fertility. In males, the mutant mouse
without A-MYB was found to be infertile, due to defects in sperm development.
"We found that the testes of the mutant male mice were
surprisingly similar to many infertile men who fail to produce
spermatozoa, linking the loss of this protein to male infertility," says
Reddy. Thirty percent of infertile men are infertile due to their
failure to produce sperm.
These studies for the first time provide an approach to correct
defects in male fertility, which would involve correcting the production
levels of A-MYB in these men. Fels researchers are currently conducting
experiments which involve gene therapy approaches that could correct this
type of male infertility.
Fels researchers are also investigating the possibility that
over-production of A-MYB may be linked to testicular cancer.
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