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View the Table of Contents for the August 15 issue of Cancer Research.
Page 7843
Zhou et al. Page 7889
Growth control pathways mediated by p53 and Rb are frequently altered in human prostate cancer. However, their roles and potential synergy in tumor progression to the metastatic phenotype are less well defined. To test directly the roles of p53 and Rb in prostate carcinogenesis, Zhou et al. conditionally inactivated these genes in the mouse prostate epithelium. Their studies demonstrated that selective inactivation of both genes results in metastatic prostate cancer. The resulting carcinomas are marked with multiple gene expression signatures commonly found in human prostate carcinomas and carry recurrent genetic alterations at loci containing Nfib, L-myc, and Nkx3.1. The new genetically defined model should be particularly valuable for providing new molecular insights into the pathogenesis and progression of human prostate cancer.
Gao et al. Page 7929
Although androgen deprivation therapy is a widely used treatment for patients with advanced prostate cancer, it ultimately results in the emergence of a hormone-refractory disease that is invariably fatal. Using a well characterized mouse model of prostate cancer, Gao et al. show that Pten loss-of-function is sufficient for androgen independence even in the absence of overt cancer progression. The findings in this mouse model demonstrate that acquisition of androgen independence can be uncoupled from overt cancer progression, and raise the possibility that hormone-refractory disease can arise at early stages of prostate carcinogenesis.
Page 8274
It has been argued that some stem cell properties observed may be due to cell-cell fusion in vivo. To test this, human adenocarcinoma cells from the pleural effusion of a breast cancer patient were injected into the mammary glands of nude mice and grown into solid tumors by Jacobsen et al. Cells derived from these tumors consisted of “activated” stroma of mouse origin and were tumorigenic. However, 30% of the cells contain mixtures of mouse and human chromosomes, or mouse/human chromosomal translocations. Hybrid nuclei were also detected in the primary xenograft. Thus, synkaryons formed in the solid tumor by spontaneous fusion between the malignant epithelium and the surrounding normal stroma, suggesting new mechanisms for tumor progression and development of drug resistance.
Page 8297
The vast majority of our knowledge about the role of BRCA1 and BRCA2 mutations in breast cancer comes from the study of high-risk, primarily white women in families with very early onset breast cancer. Malone et al. report on the prevalence and predictors of mutations in a large population-based study of breast cancer in black and white women ages 35 to 64 years with no overt family history. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status while BRCA2 predictors were fewer and more modest in magnitude.