Low expression of RECQL is associated with poor prognosis in Chinese breast cancer patients

Abstract Background RECQL is a number of the RecQ DNA helicase family and plays an important role in maintaining genome stability. Although several studies have reported that RECQL mutations were correlated with the susceptibility to breast cancer, the effect on prognosis in breast cancer was not yet clarified. Here, we explored the association between RECQL expression level and survival in patients with breast cancer. Methods In the first cohort, the RECQL mRNA expression level was evaluated in 774 primary breast cancer patients using a quantitative real-time PCR assay. Then, in the second independent cohort, the level of RECQL protein expression was detected in 322 patients with breast cancer using immunohistochemistry assay. Survival curves of patients with RECQL expression were compared using the Kaplan-Meier method with log-rank test. Results In the first cohort of 774 breast cancer patients, the low expression level of RECQL mRNA was significantly correlated with aggressive clinicopathological characteristics, including the positive lymph node status (P = 0.026), HER2 overexpression (P < 0.001), ER negative status (P = 0.047) and high tumor grade (P = 0.041). Moreover, the low expression level of RECQL mRNA was significantly associated with poor distant recurrence-free survival (DRFS, unadjusted hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.88–4.09, P < 0.001) and disease-specific survival (DSS, unadjusted HR: 3.10, 95% CI: 1.84–5.20,P < 0.001), and it remained an independent unfavorable factor for DRFS and DSS (DRFS: adjusted HR: 3.04, 95% CI: 1.89–4.87, P < 0.001; DSS: adjusted HR: 4.25, 95% CI: 2.12–8.46, P < 0.001). In the second cohort of 322 breast cancer patients, low expression of RECQL protein was also subject to poor survival in breast cancer, and it was an independent prognosis factor of poor DRFS by multivariate analysis (DRFS: adjusted HR: 2.12, 95% CI: 1.16–3.88, P = 0.015). Conclusions Breast cancer patients with low RECQL expression had a worse survival. The expression level of RECQL may be a potential prognosis factor for breast cancer

Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer

Purpose Recently, a 36-kDa variant of estrogen receptor alpha (ER-alpha 66), ER-alpha 36, has been identified and cloned. ER-alpha 36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated &quot;nongenomic&quot; signaling pathway. Here, we investigate the association between ER-alpha 36 expression and tamoxifen resistance in patients with breast cancer. Patients and Methods ER-alpha 36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay. Results In the first cohort of 710 consecutive patients, overexpression of ER-alpha 36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-alpha 66 positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-alpha 36 was not associated with survival in patients with ER-alpha 66 positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-alpha 66-negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-alpha 36 was significantly associated with poorer DFS and DSS in 156 ER-alpha 66-positive patients from this cohort, and ER-alpha 36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P = .003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018). Conclusion Women with ER-alpha 66-positive tumors that also express high levels of ER-alpha 36 are less likely to benefit from tamoxifen treatment.OncologySCI(E)PubMed76ARTICLE213423-34292

Hepatoprotective effects of raspberry (Rubus coreanus Miq.) seed oil and its major constituents

Raspberry seed is a massive byproduct of raspberry juice and wine but usually discarded. The present study employed a microwave-assisted method for extraction of raspberry seed oil (RSO). The results revealed that omega-6 fatty acids (linoleic acid and γ-linolenic acid) were the major constituents in RSO. Cellular antioxidant enzyme activity such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were investigated in HepG2 cells treated with RSO. Induction of the synthesis of several antioxidants in H2O2-exposed HepG2 cells was found. RSO increased the enzyme activity of SOD, CAT, and GPx in H2O2-exposed HepG2. Furthermore, RSO inhibited the phosphorylation of upstream mitogen-activated protein kinases (MAPK) such as c-Jun N-terminal kinase (c-JNK) and extracellular signal-regulated kinase (ERK). Taken together, the possible mechanisms to increase antioxidant enzyme activities in HepG2 may through the suppression of ERK and JNK phosphorylation. Raspberry seed oil exhibited good effects on the activities of the intracellular antioxidant enzymes and seems to protect the liver from oxidative stress through the inhibition of MAPKs. © 201

Mutations in <i>RECQL</i> Gene Are Associated with Predisposition to Breast Cancer

<div><p>The genetic cause for approximately 80% of familial breast cancer patients is unknown. Here, by sequencing the entire exomes of nine early-onset familial breast cancer patients without <i>BRCA1/2</i> mutations (diagnosed with breast cancer at or before the age of 35) we found that two index cases carried a potentially deleterious mutation in the <i>RECQL</i> gene (RecQ helicase-like; chr12p12). Recent studies suggested that <i>RECQL</i> is involved in DNA double-strand break repair and it plays an important role in the maintenance of genomic stability. Therefore, we further screened the <i>RECQL</i> gene in an additional 439 unrelated familial breast cancer patients. In total, we found three nonsense mutations leading to a truncated protein of RECQL (p.L128X, p.W172X, and p.Q266X), one mutation affecting mRNA splicing (c.395-2A>G), and five missense mutations disrupting the helicase activity of RECQL (p.A195S, p.R215Q, p.R455C, p.M458K, and p.T562I), as evaluated through an <i>in vitro</i> helicase assay. Taken together, 9 out of 448 <i>BRCA</i>-negative familial breast cancer patients carried a pathogenic mutation of the <i>RECQL</i> gene compared with one of the 1,588 controls (<i>P</i> = 9.14×10^-6). Our findings suggest that <i>RECQL</i> is a potential breast cancer susceptibility gene and that mutations in this gene contribute to familial breast cancer development.</p></div

Functional analyses of the eight missense mutations in the <i>RECQL</i> gene.

<p>(A) helicase activity of the eight <i>RECQL</i> missense mutants. The helicase-defective K119A mutant was included as a negative control. B, boiled dsDNA; UB, unboiled dsDNA; WT, wild type; double lines, dsDNA; single lines, ssDNA. (B) Quantitative analysis of the helicase assay of RECQL mutants. Helicase data represent the mean of three independent experiments with the mean±S.D. indicated by error bars. The percent unwinding of mutants were compared to the WT level. The results of an unpaired, two-tailed t-test for the mutants are shown. *p < 0.05; **p <0.01.</p