Aggressive Subclass of Prostate Cancer May be Driven By Estrogen Signaling
Aggressive prostate cancers that harbor a particular gene fusion are a distinct molecular subtype of the disease and their growth may be regulated by estrogen signaling.
Prostate cancers that carry the TMPRSS2-ERG gene fusion, which links the regulatory region of one gene to the protein-coding region of another, tend to be aggressive. The molecular mechanism by which the fusion gene impacts pathogenesis has been unknown.
Mark Rubin, M.D., of Weill Cornell Medical College in New York and colleagues examined the expression pattern of 6,144 genes in tumor samples from 455 patients from the Swedish Watchful Waiting cohort and the Physicians Health Study cohort from the United States.
Overall the investigators found that 103 tumors contained the fusion gene. When they compared the gene expression pattern in the tumors with the TMPRSS2-ERG fusion and those lacking it, they identified an 87-gene signature that correlated with the fusion gene. Many of the genes in the signature respond to estrogen signaling. In vitro experiments with prostate cancer cell lines indicated that drugs that stimulate one type of estrogen receptor (ER) promoted cancer cell growth, while drugs that activated another type of estrogen receptor (ER) increased cell death.
Our results suggest a mechanism by which prostate cancers might develop androgen independence from an initial androgen-dependent state, the authors write.
Contact: Andrew Klein, office of public affairs, Weill Cornell Medical College, email@example.com
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