Creating prostate cancer in mice
Stem or progenitor cells that can repair the prostate after injury can develop into tumors.
Most prostate tumors rely on male hormones — called androgens — to survive. Aggressive prostate cancer is often treated with drugs that block androgens, which usually cause the prostate tumors to shrink. One class of the drugs works by binding to and inactivating the androgen receptor protein on prostate cancer cells. However, aggressive prostate tumors can often become resistant to these anti-androgen therapies.
It is not clear where the resistant cancer cells come from. In 2009, researchers showed that the normal prostate contains some cells that appear to be independent of androgens. A subset of these cells — also known as CARNs — can act as stem or progenitor cells that can repair the prostate after injury. These normal androgen-independent cells can also be the cells from which prostate tumors arise. Here, Chua et al. — including one of the researchers from the 2009 study — investigated how these CARN cells behave when the androgen receptor is deleted.
When the androgen receptor was genetically removed in CARN cells of otherwise healthy mice, the behavior of CARN cells was unaffected. When the androgen receptor was deleted together with a protein that normally suppresses the formation of tumors, it protected the mice from prostate cancer. However, Chua et al. also observed that deleting the androgen receptor could not prevent the tumor from growing when two cancer-causing mutations were present. These tumors were similar to human prostate tumors that are resistant to anti-androgen therapy.
Since CARN cells may also exist in humans, this new way of making prostate cancers in mice may be used to study how these resistances arise in patients. A better understanding of how prostate tumors develop might lead to new treatments in which the androgen receptor is blocked in combination with other new protein targets.
To find out more
Read the eLife research paper on which this eLife digest is based:
