The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice

Wayne A. Fritz, Tien Min Lin, Robert Cardiff, Richard E. Peterson

Research output: Contribution to journalArticle

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Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates the inhibitory effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on prostate growth and also modulates normal prostate development. This is evidenced by AhR null mice (Ahr-/-) having smaller dorsolateral and anterior prostates, even though all prostate lobes remain histologically normal. To test the hypothesis that loss of the AhR increases the rate of prostate carcinogenesis, the incidence of macroscopic prostate tumors was determined in Ahr+/+, Ahr+/- and Ahr-/- C57BL/6J transgenic adenocarcinoma of the mouse prostate (TRAMP) mice at 35, 70, 105, 140, 175 and 210 days of age. From 140 days, prostate tumor incidence was greater in Ahr-/- (60%) and Ahr-/- (43%) mice than in Ahr+/+ mice (16%). Allele quantification did not indicate a loss of the wild-type Ahr allele in heterozygous TRAMP tumors, suggesting that tumor formation in these mice was not due to a loss of Ahr heterozygosity. Prostatic SV40 large T antigen mRNA expression and protein localization were comparable in TRAMP mice of each Ahr genotype. Prostates from all mice of each Ahr genotype were histologically indistinguishable, exhibiting diffuse epithelial hyperplasia by 105 days of age. mRNA expression and protein localization for molecular markers of neuroendocrine differentiation, including chromogranin A and neuropilin-1, were elevated in prostate tumors compared to tumor-free ventral prostates, regardless of Ahr genotype or age. Taken together, these results demonstrate that the Ahr inhibits prostate carcinogenesis in C57BL/6J TRAMP mice by interfering with neuroendocrine differentiation.

Original languageEnglish (US)
Pages (from-to)497-505
Number of pages9
JournalCarcinogenesis
Volume28
Issue number2
DOIs
StatePublished - Feb 1 2007

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Aryl Hydrocarbon Receptors
Transgenic Mice
Prostate
Carcinogenesis
Adenocarcinoma
Neoplasms
Genotype
Alleles
Neuropilin-1
Polyomavirus Transforming Antigens
Chromogranin A
Messenger RNA
Loss of Heterozygosity
Viral Tumor Antigens
Differentiation Antigens
Incidence

ASJC Scopus subject areas

  • Cancer Research

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The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice. / Fritz, Wayne A.; Lin, Tien Min; Cardiff, Robert; Peterson, Richard E.

In: Carcinogenesis, Vol. 28, No. 2, 01.02.2007, p. 497-505.

Research output: Contribution to journalArticle

Fritz, Wayne A. ; Lin, Tien Min ; Cardiff, Robert ; Peterson, Richard E. / The aryl hydrocarbon receptor inhibits prostate carcinogenesis in TRAMP mice. In: Carcinogenesis. 2007 ; Vol. 28, No. 2. pp. 497-505.
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