SOD2 Gene Variants (rs4880 and rs5746136) and Their Association with Breast Cancer Risk.

The superoxide dismutase (SOD) is the principal antioxidant defense system in the body that is activated by a reactive oxygen species. Some variants of the SOD2 gene have been associated with cancer. The rs4880 variant was determined by PCR real-time and the rs5746136 variant by PCR-RFLP in healthy subjects and in breast cancer (BC) patients. The rs4880 and rs5746136 variants were associated with BC susceptibility when BC patients and the control group were compared for the CT, TT, CTCC, and the T alleles (p < 0.05). The CT genotype of the rs4880 variant showed significant statistical differences in patients and controls aged ≤ 45 years old, and with hormonal consumption (p < 0.05). The rs4880 variant was associated with BC patients with CTTT genotype and obesity, the presence of DM2-SAH, and a non-chemotherapy response (p < 0.05). Additionally, the rs5746136 variant was associated with susceptibility to BC with Ki-67 (≥20%), luminal A type BC, and a chemotherapy partial response (p < 0.05) in BC patients who carry TT, TC, and CTTT genotypes, respectively. The haplotype T/T (OR 1.98; 95% CI 1.20−3.26, p = 0.005) was observed to be a risk factor for BC. The rs4880 and rs5746136 variants in the SOD2 gene were associated with BC susceptibility.

Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation.

BACKGROUND: WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the WNT7A gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation. METHODS: We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative WNT7A expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures. RESULTS: WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (p ≤0.001). By restoring WNT7A expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of WNT7A expression in Jurkat cells did not activate the canonical Wnt/ß-catenin pathway. CONCLUSIONS: To our knowledge, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of WNT7A as a tumor suppressor gene as well as a therapeutic tool.

Insulin glargine affects the expression of Igf-1r, Insr, and Igf-1 genes in colon and liver of diabetic rats.

OBJECTIVES: The mitogenic effect of the analogous insulin glargine is currently under debate since several clinical studies have raised the possibility that insulin glargine treatment has a carcinogenic potential in different tissues. This study aimed to evaluate the Igf-1r, Insr, and Igf-1 gene expression in colon and liver of streptozotocin-induced diabetic rats in response to insulin glargine, neutral protamine Hagedorn (NPH) insulin, and metformin treatments. MATERIALS AND METHODS: Male Wistar rats were induced during one week with streptozotocin to develop Type 2 Diabetes (T2D) and then randomly distributed into four groups. T2D rats included in the first group received insulin glargine, the second group received NPH insulin, the third group received metformin; finally, untreated T2D rats were included as the control group. All groups were treated for seven days; after the treatment, tissue samples of liver and colon were obtained. Quantitative PCR (qPCR) was performed to analyze the Igf-1r, Insr and Igf-1 gene expression in each tissue sample. RESULTS: The liver tissue showed overexpression of the Insr and Igf-1r genes (P>0.001) in rats treated with insulin glargine in comparison with the control group. Similar results were observed for the Insr gene (P>0.011) in colonic tissue of rats treated with insulin glargine. CONCLUSION: These observations demonstrate that insulin glargine promote an excess of insulin and IGF-1 receptors in STZ-induced diabetic rats, which could overstimulate the mitogenic signaling pathways.

DNA repair/replication transcripts are down regulated in patients with Fragile X Syndrome.

BACKGROUND: Fragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats. The mechanisms of repeat expansion are dependent on the presence of cis elements and the absence of trans factors both of which are not mutually exclusive and contribute to repeat instability. Expansions associated with trans factors are due to the haploinsuffient or reduced expression of several DNA repair/metabolizing proteins. The reduction of expression in trans factors has been primarily conducted in animal models without substantial examination of many of these expansion mechanisms and trans factors in humans. RESULTS: To understand the trans factors and pathways associated with trinucleotide repeat expansion we have analyzed two microarray datasets which characterized the transcript expression in patients with FXS and in controls. CONCLUSION: We observed significant down regulation of DNA damage/repair pathway transcripts. This observation was consistent in both datasets, which used different populations. Within these datasets, several transcripts overlapped in the direction of association and fold change. Further characterization of these genes will be critical to understand their role in trinucleotide repeat instability in FXS.

FMR1 protein expression in blood smears for fragile X syndrome diagnosis in a Mexican population sample.

Molecular diagnosis of fragile X syndrome (FXS) is carried out by Southern blot or polymerase chain reaction-Southern analysis; however, these procedures are expensive and time consuming, making it impractical for mass screening programs. Willemsen et al. developed and tested the diagnostic potential of a rapid antibody test on blood smears, based on the presence of fragile X mental retardation protein (FMRP) in peripheral lymphocytes from normal individuals and its absence in male patients with FXS. The diagnostic power of this antibody test is perfect for men, whereas the results are less specific for women. Validation of this procedure has been achieved mainly in the Caucasian population, but no reports including Latin American individuals have been published. To test this procedure, expression of FMRP in peripheral lymphocytes was achieved both in Mexican FXS patients and normal men and was compared with the molecular analysis of the CGG repetitive sequences of the FMR1 gene. The results of the antibody test, which measure the FMRP expression, entirely correlated with the molecular tests using polymerase chain reaction on DNA modified. Sensitivity and specificity of the test and the positive and negative predictive values were 100%. This noninvasive test requires one or two blood drops; it is rapid, simple, and inexpensive, making this procedure an ideal choice for screening large groups of male patients with mental retardation.