Endocrine disruptors fludioxonil and fenhexamid stimulate miR-21 expression in breast cancer cells.

نویسندگان

  • Yun Teng
  • Tissa T Manavalan
  • Chuan Hu
  • Svjetlana Medjakovic
  • Alois Jungbauer
  • Carolyn M Klinge
چکیده

Fenhexamid and fludioxonil are antifungal agents used in agricultural applications, which are present at measurable amounts in fruits and vegetables. Fenhexamid and fludioxonil showed endocrine disruptor activity as antiandrogens in an androgen receptor reporter assay in engineered human breast cancer cells. Little is known about how environmental chemicals regulate microRNA (miRNA) expression. This study examined the effect of fenhexamid and fludioxonil on the expression of the oncomiR miR-21 in MCF-7, T47D, and MDA-MB-231 human breast cancer cells and downstream targets of miR-21 in MCF-7 cells. Fenhexamid and fludioxonil stimulated miR-21 expression in a concentration-dependent manner and reduced the expression of miR-21 target Pdcd4 protein. Antisense to miR-21 blocked the increase in Pdcd4 protein by fenhexamid and fludioxonil. Fenhexamid and fludioxonil reduced miR-125b and miR-181a, demonstrating specificity of miRNA regulation. Induction of miR-21 was inhibited by the estrogen receptor antagonist fulvestrant, by androgen receptor antagonist bicalutamide, by actinomycin D and cycloheximide, and by inhibitors of the mitogen-activated protein kinases and phosphoinositide 3-kinase pathways. Fenhexamid activation was inhibited by the arylhydrocarbon receptor antagonist α-napthoflavone. Fenhexamid and fludioxonil did not affect dihydrotestosterone-induced miR-21 expression. Fludioxonil, but not fenhexamid, inhibited MCF-7 cell viability, and both inhibited estradiol-induced cell proliferation and reduced cell motility. Together these data indicate that fenhexamid and fludioxonil use similar and distinct mechanisms to increase miR-21 expression with downstream antiestrogenic activity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Deregulation of miR-21 and miR-155 and their putative targets after silibinin treatment in T47D breast cancer cells

Objective(s):MicroRNAs (miRNAs) are a class of short RNAs that control the biological processes including cell proliferation, apoptosis and development. Aberrant expression of miRNAs was determined in the different stages of tumor development and metastasis. To study the effect of silibinin on miRNAs expression, we evaluated quantitative expression of miR-21 and miR-155 as two oncomiRs and seve...

متن کامل

Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells

Objective(s): Despite the good results of anticancer activities by curcumin, there are some hurdles that limit the use of curcumin as an anticancer agent. Many methods were examined to overcome this defect like the use of the dendrosomal curcumin (DNC). There is increasing evidence that miRNAs play important roles in biological processes. In this study, we focus on the roles of microRNA-21 in t...

متن کامل

Inhibition of breast cancer metastasis by co-transfection of miR-31/193b-mimics

Objective(s): Various studies have been conducted to reduce the metastatic behavior of cancerous cells. In this regard, ectopic expression of anti-metastatic microRNAs by miR-mimic and miR-restoration-based therapies could bring new insights to the field. In the present study, the consequences of co-transfecting breast cancer cell lines with miR-193b and miR-31 were investigated via invasion an...

متن کامل

Correlation between Expression of hsa-miR-490-5p and NFAT5 in Peripheral Blood Mononuclear Cell Obtained from Breast Cancer Patients

Breast cancer is a complex genetic disease that has an average annual incidence of two million people and the second leading cause of death among women all over the world. Micro-RNAs are consistently reported to regulate gene expression in all cancers. The present study, the correlation between the expression of hsa-miR-490-5p and nuclear factor of activated T-cells 5 (NFAT5) in breast cancer w...

متن کامل

Mir-183 and FOXO1 gene expression changes in peripheral blood mononuclear cells of breast cancer patients

Background and Aim: Today, cancer is considered as a major health problem and affects the health of society. Breast cancer is the second leading cause of cancer death in women after lung cancer. According to epidemiological studies, cancer is the second most common cause of death after cardiovascular disease worldwide and the third leading cause of death after cardiovascular disease and acciden...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Toxicological sciences : an official journal of the Society of Toxicology

دوره 131 1  شماره 

صفحات  -

تاریخ انتشار 2013