Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes
نویسندگان
چکیده
Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97.6%) samples tested. Interestingly, our studies reveal that Pax-5 inhibits aggressive features and confers anti-proliferative effects in breast carcinoma cells in contrast to its oncogenic properties in B cell cancers. More precisely, Pax-5 suppressed breast cancer cell migration, invasion and tumor spheroid formation while concomitantly promoting cell adhesion properties. We also observed that Pax-5 inhibited and reversed breast cancer epithelial to mesenchymal phenotypic transitioning. Mechanistically, we found that the Pax-5 transcription factor binds and induces gene expression of E-cadherin, a pivotal regulator of epithelialisation. Globally, we demonstrate that Pax-5 is predominant expressed factor in mammary epithelial cells. We also present an important role for Pax-5 in the phenotypic transitioning processes and aggressive features associated with breast cancer malignancy and disease progression.
منابع مشابه
بررسی فراوانی بروز مارکرهای E-Cadherin , Dysadherinدر کارسینوم های پستان
Background and purpose: Breast carcinoma is the most common malignant tumor and the leading cause of death due to cancer among women. Previous studies have shown that increased expression of dysadherin promotes cancer metastasis and reduced expression of E-cadherin was also associated with progression of epithelial tumors. The aim of this study was concurrent assessment of E- cadherin and dysad...
متن کاملBreast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways
The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues...
متن کاملHypermethylation of E-Cadherin and Estro-gen Receptor- Gene Promoter and Its Association with Clinicopathological Features of Breast Cancer in Iranian Patients
Background: Aberrant methylation of cytosine-guanine dinucleotide islands leads to inactivation of tumor suppressor genes in breast cancer. Tumor suppressor genes are unmethylated in normal tissue and often become hypermethylated during tumor formation, leading to gene silencing. We investigated the association between E-cadherin (CDH1) and estrogen receptor-α (ESRα) gene promoter methylation a...
متن کاملSilencing of rhomboid domain containing 1 to inhibit the metastasis of human breast cancer cells in vitro
Objective(s): A growing body of evidence indicates that rhomboid domain containing 1 (RHBDD1) plays an important role in a variety of physiological and pathological processes, including tumorigenesis. We aimed to determine the function of RHBDD1 in breast cancer cells. Materials and Methods: In this study, we used the Oncomine™ database to determine the expression patterns of RHBDD1 in normal a...
متن کاملThe Effect of Interval Training on the Expression of Tumor Suppressor Gene, Systemic Inflammation, and Tumor Volume in Breast Cancer–Bearing BALB/c Mice
Introduction: E-cadherin is expressed in most normal epithelial tissues. Loss of E-cadherin can cause dedifferentiation and invasiveness in human carcinomas, leading E-cadherin to be classified as a tumor suppressor. Therefore, the aim of this study was to investigate the effect of interval training on the expression of tumor suppressor gene E-cadherin in breast cancer-bearing BALB/c mice. Meth...
متن کامل