Prostata 10 Min
Prostate cancer escapes control and turns deadly when the malignant cells start listening to the wrong hormones, Stanford researchers have discovered. The results explain why prostate cancer eventually becomes impervious to a commonly used kalzinieren in der Prostata.
These hormones deliver a strong message to a prostate cancer cell: Be fruitful and multiply. As they reproduce, the cells spill out a protein marker called prostate specific antigen, or PSA. Though it sounds extreme, the treatment usually works as long as the tumor remains "androgen-dependent," or requires androgens to grow, Feldman said. But unless the patient dies of something else first, Feldman said, the cancer eventually metamorphoses into an "androgen-independent" state in which it can grow without stimulation from these hormones.
No longer halted by castration or androgen deprivation, the cancer begins to proliferate, and currently there are no other treatments to stop it from spreading to the bones or other organs and eventually killing the patient.
About 40, American men die every year from androgen-independent prostate cancer. Among cancers, only lung cancer kills more men. What transforms the cancer from treatable to untreatable? To find out, the researchers began studying a lineage of metastatic prostate cancer cells isolated from a patient who later died from the disease. Initial experiments suggested there was a defect in the cells' responsiveness to androgens. So Feldman and his team sequenced the gene for the androgen receptor, a protein in the cell's nucleus that functions as an androgen sensor.
Androgens latch onto the receptor molecule, triggering metabolic changes within the cell that stimulate cell division. Writing in the Kalzinieren in der Prostata issue of Nature Medicine, Feldman and colleagues report that the androgen receptor gene in the metastatic cancer cells contained two mutations that transformed its activity.
Androgens no longer bound tightly to the receptor. Instead, cortisol and cortisone, the body's "stress hormones," did. Kalzinieren in der Prostata released in large amounts during stressful situations, cortisol and cortisone also help regulate metabolism during quieter times and are secreted continually by the adrenal glands atop the kidneys. Presumably, the mutations contorted the receptor molecule into a new shape that closely matched the shapes of cortisone and cortisol.
By recreating the mutant receptors in the laboratory, Feldman and his colleagues proved that the double mutation converted the androgen receptor into a receptor that responds inappropriately to cortisol, cortisone and other hormones. To show that the mutated cancer cells responded to the cortisone and cortisol, Feldman's team grew the cells in a culture medium and exposed them to increasing doses of the hormones. For patients, this change in the shape of the androgen receptor would bring on disaster.
Levels of cortisone and cortisol in the body are high enough to keep the cells permanently stimulated, Feldman noted. That means that the prostate cancer cells are deluged with signals to divide, which could account for their rapid multiplication in later-stage cancers.
However, Feldman added, the team is not sure yet how common these mutations are among prostate cancer patients. Some kalzinieren in der Prostata news emerged kalzinieren in der Prostata the study. Though it would be difficult to banish cortisol and cortisone from kalzinieren in der Prostata patient's body without creating further problems, it may be possible to block the mutated androgen receptor and prevent these hormones from stimulating growth of cancer cells.
Feldman and colleagues are already pondering ways to do this. Anderson Cancer in Houston also collaborated with the Stanford team. Army Medical Research Acquisition Activity. All Rights Reserved. StanfordCA