Scientists at the Hopkins School of Medicine have found that the malignant cells that cause prostate cancer in adults behave very similarly to normally developing prostate cells on a genetic level. This finding provides a link between cancer biology and developmental biology that could lead to important insights for both fields.
The team, led by associate professor of pathology, oncology and urology David Berman, found that many of the genes involved in prostate formation in infant mice have counterparts in the genes involved in human prostate cancers.
Because prostate development is well-characterized and traceable, their work has deepened our understanding of cancers and opened up new avenues for treatment of prostate cancer.
"We knew that cancers and developing organs looked similar under the microscope," Berman said. "But we didn't know that they used highly related molecular programs. This study rigorously tested and confirmed this hypothesis."
Scientists have noticed since the 1920s that cancers behave much like embryonic cells - both types grow very quickly, can spread and invade nearby tissues, are resistant to aging and death and have a high ability to recruit blood vessels to supply them with nutrients - but in cancers, these characteristics are ultimately destructive.
Berman's lab took advantage of this fact to study the genetic behavior of prostate cancer.
Androgens, which are male hormones including testosterone, signal the prostate gland to develop in male embryos. Scientists artificially injected pregnant female mice with androgens, which also triggers prostate development in female embryos.
Within 48 hours of injection, they used a mouse gene chip to see which genes were being expressed and which genes were suppressed in the androgen-exposed female embryos compared to normal females and males.
A total of 829 mouse genes were found to change their activity in response to androgen hormones, either by increasing or decreasing expression.
The team then compared the mouse genes shown to be important in prostate development to the human counterparts that are known to be involved in prostate cancer and found that many of the genes are either turned on or off at different stages in the disease, but are definitely significantly involved.
These genes are most involved during transition stages as the cancer becomes more aggressive. "The particular genes that were regulated in response to androgens in development were the same genes that were regulated differently as human prostate cancers progressed from precancerous lesions to invasive cancer to metastatic cancer," Berman said.
Berman's team has found a viable new method to test genes and pathways in prostate cancer, and they plan to hone in on several of the new pathways they discovered in the hopes of contributing to new prostate cancer-specific therapies.
Prostate cancer is the most common cancer in men. About 186,000 cases develop in the U.S. each year, usually in those over 50.
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