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View the Table of Contents for the December 15 issue of Cancer Research.
Pekarsky et al. Page 11590
B-cell Chronic Lymphocytic Leukemia (BCLL) is the most common human leukemia in the world. Deregulation of the TCL1 oncogene is a causal event in the pathogenesis of the aggressive form of this disease, as was verified by using animal models. To study the mechanism of Tcl1 regulation in CLL, Pekarsky et al. carried out microRNA expression profiling of three types of CLL: indolent CLL, aggressive CLL, and aggressive CLL showing 11q deletion. Distinct microRNA signatures corresponding to each group of CLL were identified. The authors determined that Tcl1 expression is regulated by miR-29 and miR-181, two microRNAs differentially expressed in CLL. Expression level of miR-29 and miR-181 generally inversely correlated with Tcl1 expression in CLL samples. The results suggest that Tcl1 expression in CLL is at least partially regulated by miR-29 and miR-181, and that these miRNAs may be candidates for therapeutic agents in CLLs overexpressing Tcl1.
Nakagawa et al. Page 11825
To determine if protein expression patterns in primary breast cancers can predict axillary lymph node (ALN) metastasis, Nakagawa et al. assessed differences in protein expression between primary breast cancers with and without ALN metastasis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). A significant proteomic signature was detected when comparing patients with negative ALN, those with ≥ 2 positive ALN or non-sentinel lymph node metastases. The use of SELDI-TOF-MS for the detection of differential protein peak expression in primary breast cancers has utility and may help predict the presence and number of axillary lymph node metastases and also the status of non-sentinel lymph nodes.
Takahashi et al. Page 11932
To elucidate the mechanism of acquired resistance to Adriamycin, Takahashi et al. searched for genes that, when overexpressed, render Saccharomyces cerevisiae resistant to Adriamycin. The authors identified AKL1, a gene of which the function is unknown, but is considered to be a member of the Ark/Prk kinase family, which is involved in the regulation of endocytosis. The uptake of the lucifer yellow fluorescent dye as a marker for transport demonstrated that the AKL1 kinase activity is required for both the Adriamycin resistance and the endocytic activity of yeast cells. The authors also found that HEK293 cells that overexpressed AAK1, a member of the human Ark/Prk family, were Adriamycin resistant. These findings suggest that the endocytic pathway might be involved in the mechanism of Adriamycin toxicity in yeast and human cells.
Kim et al. Page 12009
RXR-selective ligands (or "rexinoids") are effective cancer prevention agents with reduced toxicity compared to retinoids. Kim et al. used microarray analysis to identify target genes modulated by rexinoids in human breast cells. Genes modulated by the cancer-preventive retinoid bexarotene included ID-1, IGFBP-6, and SCD-1 (induced) and cyclin D1 and Cox-2 (suppressed). The modulation of these genes may be critical for rexinoid-induced growth suppression and cancer prevention. These studies provide the preclinical rationale to use these rexinoid-regulated genes as biomarkers of the effect of rexinoids in clinical trials and also as potential targets of novel cancer preventive drugs.
Setiawan et al. Page 12019
The CYP11A gene has a key role in steroid hormone biosynthesis. Setiawan et al. employed a systematic approach including gene resequencing and haplotype analysis to investigate the relationship between common variations in CYP11A and breast cancer risk in five racial/ethnic populations in the Multiethnic Cohort comprised of over 215,000 individuals. A global test for differences in risk according to common haplotypes over the locus was statistically significant as were associations with haplotypes in each block (i.e. region of strong linkage disequilibrium). These haplotype effects on risk across each ethnic group were homogeneous. Thus, CYP11A deserves further consideration as a candidate breast cancer susceptibility gene and follow-up in other large study populations is warranted.