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View the Table of Contents for the January 1 issue of Cancer Research
Page 54
Wetherill et al. demonstrate that exposure to the xenoestrogen bisphenol A (BPA) impacts androgen receptor (AR)-dependent gene expression and proliferation in prostate cancer cells. Tumor-derived AR alleles were activated by BPA, and incidental levels of BPA cooperated with endogenous androgen to enhance receptor activity. By contrast, high-level exposure blocked cellular proliferation exclusively in AR-positive cells. Combined, these data indicate that BPA influences AR function and resultant tumor cell proliferation. Given the importance of AR as a target in prostate cancer therapy, these results provide the impetus to monitor the impact of BPA on therapeutic intervention.
Page 92
The Rassf1a gene, located at 3p21.3, is frequently silenced by DNA methylation in a variety of human solid tumors. Tommasi et al. documented that Rassf1a knockout mice were prone to spontaneous tumorigenesis at advanced age. Rassf1a-/- and Rassf1a+/- mice showed increased tumor multiplicity and tumor size relative to control animals when treated with two chemical carcinogens, benzo[a]pyrene and urethane, to induce skin and lung tumors, respectively. The data are consistent with a tumor-suppressive role of Rassf1a, which may explain its frequent epigenetic inactivation in human tumors.
Page 166
The APC tumor suppressor is a major regulator of the Wnt signaling pathway in normal intestinal epithelium. In order to discover novel genes that may contribute to tumor progression in the gastrointestinal tract, Reichling et al. used cDNA microarrays to identify 114 genes with altered levels of expression in ApcMin mouse adenomas from the duodenum, jejunum and colon. Changes in the expression of 24 of these 114 genes were not observed during mouse development at embryonic day 16.5, postnatal day 1, or postnatal day 14 (relative to normal adult intestine). These 24 genes are not previously known Wnt targets.
Page 325
Many cancers arise as a consequence of a gradual accumulation of genetic aberrations, each disorder conferring survival advantage. The recently identified DNA polymerase κ is an error-prone enzyme which is up-regulated in lung cancers possibly because its capacity to replicate smoke-induced damaged DNA induces DNA breaks. Bavoux et al. report that the overexpression of DNA polymerase κ stimulates DNA exchanges as well as loss of chromosomes, and favors tumorigenesis. These data suggest that altered DNA replication might be related to cancer-associated genetic changes.
Page 358
Intrauterine and perinatal factors have been linked to risk of cancer at several sites in the offspring. The pool of stem cells in target tissue has been suggested as a critical factor linking early life exposures to cancer. Baik et al. examined the relation between intrauterine hormone levels and measurements of stem cell potential in umbilical cord blood. We found strong positive associations between insulin-like growth factor (IGF)-1 and CD34+, CD34+CD38-, and CFU-GM. Similar associations were observed for IGFBP-3, estriol, and testosterone. These findings point to potential mechanisms that may underlie prenatal origin of cancer risk.