scholarly journals Telomere length variation in normal epithelial cells adjacent to tumor: potential biomarker for breast cancer local recurrence

2011 ◽  
Vol 33 (1) ◽  
pp. 113-118 ◽  
Author(s):  
X. Zhou ◽  
A. K. Meeker ◽  
K. H. Makambi ◽  
O. Kosti ◽  
B. V. S. Kallakury ◽  
...  
PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39011 ◽  
Author(s):  
Xin Zhou ◽  
Catalin Marian ◽  
Kepher H. Makambi ◽  
Ourania Kosti ◽  
Bhaskar V. S. Kallakury ◽  
...  

2017 ◽  
Vol 243 (4) ◽  
pp. 407-417 ◽  
Author(s):  
Li-Jie Ma ◽  
Xiao-Ying Wang ◽  
Meng Duan ◽  
Long-Zi Liu ◽  
Jie-Yi Shi ◽  
...  

2021 ◽  
Author(s):  
Natascia Marino ◽  
Rana German ◽  
Ram Podicheti ◽  
Pam Rockey ◽  
George E. Sandusky ◽  
...  

Abstract Background: Family with sequence similarity 83 member A (FAM83A) presents oncogenic properties in several cancers including breast cancer (BC). Recently, we reported FAM83A overexpression in normal breast tissues from women at high risk of breast cancer. We now hypothesize that FAM83A is a key factor in BC initiation. Methods: Immunohistochemical staining was used to evaluate FAM83A protein levels in both a normal breast tissue microarray (TMA, N=411) and a breast tumor TMA (N=349). EGFR staining and its correlation with FAM83A expression were also assessed. Lentivirus-mediated manipulation of FAM83A expression in primary and hTERT-immortalized breast epithelial cells was employed. Biological and molecular alterations upon FAM83A overexpression/downregulation and FAM83A’s interaction partners were investigated.Results: TMA analysis revealed a 1.5-fold increase in FAM83A expression level in BC cases as compared with normal breast tissues (p<0.0001). FAM83A protein expression was directly correlated with EGFR level in both normal and BC tissues. In in vitro assays, exogenous expression of FAM83A in either primary or immortalized breast epithelial cells promoted cell viability and proliferation. Additionally, Ingenuity Pathway Analysis (IPA) revealed that in normal cells FAM83A is involved in cellular morphology and metabolism. Mass spectrometry analysis identified DDX3X and LAMB3 as potential FAM83A interaction partners in primary cells, while we detected FAM83A interaction with cytoskeleton reorganization factors, including LIMA1, MYH10, PLEC, MYL6 in the immortalized cells.Conclusions: This study shows that FAM83A promotes metabolic activation in primary epithelial cells and survival in immortalized cells. These findings support its role in early breast oncogenesis.


2010 ◽  
Author(s):  
Xin Zhou ◽  
Alan Meeker ◽  
Bhaskar Kallakury ◽  
Mary Sidawy ◽  
Christopher Loffredo ◽  
...  

Mutagenesis ◽  
2020 ◽  
Author(s):  
Michal Kroupa ◽  
Sivaramakrishna Rachakonda ◽  
Veronika Vymetalkova ◽  
Kristyna Tomasova ◽  
Vaclav Liska ◽  
...  

Abstract Disruption of telomere length (TL) homeostasis in peripheral blood lymphocytes has been previously assessed as a potential biomarker of breast cancer (BC) risk. The present study addressed the relationship between lymphocyte TL (LTL), prognosis and clinicopathological features in the BC patients since these associations are insufficiently explored at present. LTL was measured in 611 BC patients and 154 healthy controls using the monochrome multiplex quantitative Polymerase Chain Reaction assay. In addition, we genotyped nine TL-associated single-nucleotide polymorphisms that had been identified through genome-wide association studies. Our results showed that the patients had significantly (P = 0.001, Mann–Whitney U-test) longer LTL [median (interquartile range); 1.48 (1.22–1.78)] than the healthy controls [1.27 (0.97–1.82)]. Patients homozygous (CC) for the common allele of hTERT rs2736108 or the variant allele (CC) of hTERC rs16847897 had longer LTL. The latter association remained statistically significant in the recessive genetic model after the Bonferroni correction (P = 0.004, Wilcoxon two-sample test). We observed no association between LTL and overall survival or relapse-free survival of the patients. LTL did not correlate with cancer staging based on Union for International Cancer Control (UICC), The tumor node metastasis (TNM) staging system classification, tumour grade or molecular BC subtypes. Overall, we observed an association between long LTL and BC disease and an association of the hTERC rs16847897 CC genotype with increased LTL. However, no association between LTL, clinicopathological features and survival of the patients was found.


2020 ◽  
Author(s):  
Lungwani Muungo

Purpose: Estrogen-responsive finger protein (Efp) is amember ofRINGfinger-B box-Coiled Coilfamily and is also a downstream target of estrogen receptor a. Previously, Efp was shown tomediate estrogen-induced cell growth, which suggests possible involvement in the developmentof human breast carcinomas. In this study, we examined expression of Efp in breast carcinomatissues and correlated these findings with various clinicopathologic variables.Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistryand laser capture microdissection/real-time PCR of Efp. Immunohistochemistryfor Efp was also done in 151breast carcinoma specimens fixed with formalin and embedded inparaffinwax.Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantlyassociated with the mRNA level (n = 30). Efp immunoreactivity was positively associated withlymph node status or estrogen receptor a status and negatively correlated with histologic gradeor 14-3-3j immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlatedwith poor prognosis of breast cancer patients, and multivariate analyses of disease-freesurvival and overall survival for151breast cancer patients showed that Efp immunoreactivity wasthe independentmarker.Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor inbreast cancer patients. These findings may account for an oncogenic role of Efp in the tumorprogression of breast carcinoma.


2020 ◽  
Vol 20 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Fang Peng ◽  
Chuansheng Yang ◽  
Yanan Kong ◽  
Xiaojia Huang ◽  
Yanyu Chen ◽  
...  

Background: CDK12 is a promising therapeutic target in breast cancer with an effective ability of maintaining cancer cell stemness. Objective: We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness. Methods: CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity. Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined. Western blot further characterized the mechanism of CDK12 in breast cancer stemness through the c-myc/β-catenin pathway. Results: Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively expressed with CDK12. The c-myc/β-catenin signaling was activated by CDK12, which is a potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker of breast cancer prognosis. Conclusion: CDK12 overexpression promotes breast cancer tumorigenesis and maintains the stemness of breast cancer by activating c-myc/β-catenin signaling. Inhibiting CDK12 expression may become a potential therapy for breast cancer.


2020 ◽  
Vol 20 (17) ◽  
pp. 2053-2065
Author(s):  
Ranliang Cui ◽  
Chaomin Wang ◽  
Qi Zhao ◽  
Yichao Wang ◽  
Yueguo Li

Background: The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3. Methods: Seventy samples of breast cancer with lymph node metastasis, seventy-three samples of nonmetastatic breast cancer and twenty-five samples of healthy human serum were collected. Serum CA15-3 concentration was determined by Roche Elecsys, and serum CPN1 concentration was determined by ELISA. Results: In breast cancer patients, serum CPN1 concentration was positively correlated with tumour size, clinical stage and CA15-3 concentration (r = 0.376, P<0.0001). ROC curve analysis showed that the optimal critical concentration of CPN1 for breast cancer diagnosis was 32.8pg/ml. The optimal critical concentration of CPN1 in the diagnosis of metastatic breast cancer was 66.121pg/ml. CPN1 has a greater diagnostic ability for breast cancer (AUCCA15-3=0.702 vs. AUCCPN1=0.886, P<0.0001) and metastatic breast cancer (AUCCA15-3=0.629 vs. AUCCPN1=0.887, P<0.0001) than CA15-3, and the combined detection of CA15-3 and CPN1 can improve the diagnostic efficiency for breast cancer (AUCCA15-3+CPN1=0.916) and for distinguishing between metastatic and non-metastatic breast cancer (AUCCA15-3+CPN1=0.895). Conclusion: CPN1 can be used as a new tumour marker to diagnose and evaluate the invasion and metastasis of breast cancer. The combined detection of CPN1 and CA15-3 is more accurate and has a certain value in clinical application.


Sign in / Sign up

Export Citation Format

Share Document