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Department of Mathematics, University of Chicago, Chicago, Illinois, USA
1 Correspondence: Department of Mathematics, University of Chicago, 5734 S. University Ave., Chicago, IL 60637, USA. E-mail: ed{at}math.uchicago.edu
Ricke et al. (1)
presented elegant evidence that the presence of estrogen receptor-
is essential for hormonal carcinogenesis in prostate cancer. This is consistent with my model (2)
for prostate cancer, which concluded that hormonal carcinogenesis in vivo might be initiated by the binding of estradiol (E2) to estrogen receptor- homodimers as well as by the binding of E2 to estrogen receptor-β heterodimers. If high local levels of E2 can initiate prostate cancer, then aromatase activity must be involved, as aromatase converts testosterone to E2. Although aromatase activity is not present in normal prostate epithelial cells, it is present in prostate cancer cell lines (3)
and in almost all prostate cancer tumors (4)
. If aromatase is not present in normal prostate cells as a result of methylation of the DNA comprising the aromatase gene, then this might explain why prostate cancer is so common in men. Although almost all other cancers require an initial mutation, prostate cancer may be started by an initial mutation or by the failure to methylate the aromatase gene.
This is not to say that the expression of aromatase always leads to prostate cancer. In fact, aromatase activity has been observed in most cases of benign prostatic hyperplasia (4)
. High levels of E2 up-regulate telomerase activity in normal prostate epithelial cells (5)
. Also, there is a proliferative response to estrogen in the prostate glands of mice except for those lacking estrogen receptor- (6)
. This makes it likely that those normal prostate epithelial cells continually exposed to high local levels of E2 may become immortalized. It still requires one or more key mutations to produce prostate cancer, but the more cells that are dividing, the greater the chance that such mutations will occur in at least one cell.
Ricke et al. (1)
stated in their discussion that "the nonaromatizable androgen DHT in combination with E2 is not sufficient to induce carcinogenesis" and gave three references to support this statement. However, none of these references mentions the use of dihydrotestosterone (DHT) in combination with E2. A careful reading of these references suggests that what the authors may have meant to say was that neither the nonaromatizable androgen DHT by itself nor E2 by itself is sufficient to induce carcinogenesis.
FOOTNOTES
The opinions expressed in editorials, essays, letters to the editor, and other articles comprising the Up Front section are those of the authors and do not necessarily reflect the opinions of FASEB or its constituent societies. The FASEB Journal welcomes all points of view and many voices. We look forward to hearing these in the form of op-ed pieces and/or letters from its readers addressed to journals@faseb.org.
REFERENCES
signaling. FASEB J. 22,1512-1520Related Article
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