Association between Lymph Node Status and Expression Levels of Androgen Receptor, miR-185, miR-205, and miR-21 in Breast Cancer Subtypes

Abstract

Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs’ expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples (n=89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.

Associations between the Levels of Estradiol-, Progesterone-, and Testosterone-Sensitive MiRNAs and Main Clinicopathologic Features of Breast Cancer

“…We have also previously shown miR-21 levels in HER2-expressing BC may be associated with the presence of LNM [11]. Here, when using a larger sample, we observed only a tendency to an increase in the miR-21 level in the tissues of patients with LNM compared to cases without, in HER2-expressing BC with Ki-67 ≥ 14%.…”

“…According to previous studies, AR expression correlates with ER status [40]. We have also previously shown that in luminal B HER2 0 BC, AR level is higher for tumors with ER IHC scores of 6-8 compared to tumors with ER IHC scores of 0-5 [11]. Considering that miR-200b is an AR-regulated miRNA, the observed decrease in its levels in tumors with lower ER levels may be due to lower AR expression.…”

Expression of estrogen‐, progesterone‐, and androgen‐responsive genes in MCF‐7 and MDA‐MB‐231 cells treated with o,pʹ‐DDT, p,pʹ‐DDT, or endosulfan

“…We also found that under the action of p , p ′‐DDT, the expression of ER, PR, and AR decreases after 48 h. In general, low expression of these receptors in luminal breast cancer subtypes correlates with a more aggressive course of the disease and a worse prognosis. [ 46–49 ] After incubation with 1 μM endosulfan, PR expression decreased after 48 h and AR expression decreased after 24 h. In contrast, under the influence of o , p ′‐DDT, the level of AR mRNA slightly increased. Both testosterone and estradiol treatment resulted in ER underexpression but PR overexpression.…”

Tumor suppressor PTEN regulation by tobacco smoke in lung squamous-cell carcinoma based on bioinformatics analysis

“…Previously published protocols were used for miRNA and total RNA isolation, miRNA and RNA reverse transcription, and real-time PCR to determine miRNA and mRNA levels [ 15 ]. Total RNA was isolated using the TRIzol™ reagent (Invitrogen, USA).…”