Estradiol shows anti-skin cancer activities through decreasing MDM2 expression.

Abstract

Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

• Authors: Li Li, Jianguo Feng, Ying Chen, Shun Li, Mengting Ou, Weichao Sun, Liling Tang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 5 Pg. 8459-8474 (Jan 31 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28035066 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Heterogeneous Nuclear Ribonucleoprotein A1
• hnRNPA1 protein, human
• Estradiol
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation
• Epithelial-Mesenchymal Transition (drug effects)
• Estradiol (pharmacology)
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Heterogeneous Nuclear Ribonucleoprotein A1 (genetics, metabolism)
• Humans
• Male
• Melanoma (drug therapy, genetics, metabolism, pathology)
• Mice, Nude
• Proto-Oncogene Proteins c-mdm2 (genetics, metabolism)
• RNA Interference
• Signal Transduction (drug effects)
• Skin Neoplasms (drug therapy, genetics, metabolism, pathology)
• Time Factors
• Transfection
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays