Researchers at the
Hopkins Kimmel Cancer Center have for the first time
implicated the muscle protein myosin VI in the development
of prostate cancer and its spread.
In a series of lab studies with human prostate cancer
cells, the Johns Hopkins scientists were surprised to find
overproduction of myosin VI in both prostate tumor cells
and precancerous lesions. When the scientists genetically
altered the cells to "silence" myosin VI, they discovered
the cells were less able to invade in a test tube.
"Our results suggest that myosin VI may be critical in
starting and maintaining the malignant properties of the
majority of human prostate cancers diagnosed today," said
Angelo M. De Marzo, a study co-author and associate
The Johns Hopkins work, published in the November
issue of The American Journal of Pathology, has
potential value for better ways to diagnose the disease,
treat and track the effects of drugs, and surgery.
Jun Luo, senior author of the paper and assistant
urology, said, "Targeting myosin VI represents a
promising new approach that could lead eventually to new
approaches to treating the disease."
Myosins are a class of 40 motor proteins that power
cell movement and muscle contractions. Normally, as they
work, myosins slide in a single direction along the threads
of a protein called actin. But myosin VI moves against the
grain, and it does not function as a classic "muscle"
Using a DNA microarray to study all the genes in 59
samples of benign or cancerous prostate tissue from
patients at Johns Hopkins, the researchers found the
malignant samples showed a 3.7-fold higher expression of
myosin VI as compared to normal samples, and a 4.6-fold
increase as compared to the samples from patients with
Next, the researchers hunted for myosin VI in 240
prostate tissue samples, discovering overproduction early
in the development of prostate cancer in such pre-tumor
conditions as high-grade prostatic intraepithelial
neoplasia and proliferative inflammatory atrophy.
Finally, when they altered some cancerous cells by
knocking down their myosin VI protein, the cancer cells not
only were less able to spread around but also showed 10
times the amount of a tumor suppressor called
Prostate cancer, which affects one in nine American
men over the course of their lives, is mainly diagnosed by
needle biopsy of the prostate gland after a blood test
shows an increased level of prostate-specific antigen.
While the PSA test is now widespread and provides many men
with early diagnosis and better chance of a cure, Luo said,
it may not be sensitive or specific enough to pinpoint the
existence of cancer. Using myosin VI or other factors, it
may be possible, Luo said, to create a laboratory test to
identify high or low levels in urine or blood samples, and
this might aid in the detection of prostate cancer. Myosin
VI also has been shown to be associated with ovarian
The study was supported by the Department of Defense,
National Cancer Institute, Donald and Susan Sturm
Foundation and Prostate Cancer Foundation. Co-authors were
Thomas A. Dunn, Shenglin Chen, Dennis A. Faith, Jessica L.
Hicks, Elizabeth A. Platz, Yidong Chen, Charles M. Ewing,
Jurga Sauvageot and William B. Isaacs.