Liver kinase B1 expression (LKB1) is repressed by estrogen receptor alpha (ERα) in MCF-7 human breast cancer cells
| Autor: | Stephanie Zantinge, Gurmit Singh, Katja Linher-Melville |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Biophysics Repressor Breast Neoplasms Protein Serine-Threonine Kinases Biology Biochemistry AMP-Activated Protein Kinase Kinases Cell Line Tumor Humans RNA Small Interfering skin and connective tissue diseases Molecular Biology Transcription factor Hormone response element Kinase Estrogen Receptor alpha Promoter Cell Biology Transfection Gene Expression Regulation Neoplastic Gene Knockdown Techniques Cancer cell Cancer research Female Estrogen receptor alpha |
| Zdroj: | Biochemical and Biophysical Research Communications. 417:1063-1068 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2011.12.096 |
| Popis: | Background Liver kinase 1 (LKB1) is emerging as a multifunctional protein, acting as a key metabolic enzyme, regulator of cell polarity, and transcription factor. Altered LKB1 expression has been linked with various cancers and may be a potential prognostic marker. While the functional role of LKB1 continues to undergo intensive investigation, the molecular mechanisms that regulate its expression remain to be defined more clearly. Recent reports have established a possible link between estrogen receptor alpha (ERα) signaling and LKB1 in MCF-7 human breast cancer cells. The current study aimed to investigate whether LKB1 is transcriptionally regulated by ERα in MCF-7 cells. Methods siRNA transfections were used to transiently knock down LKB1 and ERα. LKB1 and ERα mRNA and protein levels were evaluated by real-time PCR and Western blotting, respectively. An approximately 3 kilobase pair human LKB1 promoter construct and various truncations were generated, transfected into MCF-7 cells, and luciferase reporter assays were performed. Cells were also treated with various doses of 17-β-estradiol (E2) to evaluate the effect on LKB1 and ERα mRNA levels. Results LKB1 mRNA and protein levels were significantly lower in ERα-positive MCF-7 compared to ERα-negative MDA-MB-231 breast cancer cells, suggesting that ERα may act as a repressor. siRNA-mediated knock-down of ERα in MCF-7 cells significantly increased LKB1 promoter activity and expression at the mRNA and protein levels, and computational analysis revealed the presence of several putative estrogen response element (ERE) DNA binding sites in the LKB1 promoter region. In addition, treatment with E2 led to an increase in LKB1 expression, concomitant with decreased expression of ERα in MCF-7 cells. The E2-mediated increase was abrogated by pretreatment with actinomycin D, supporting that the observed changes in LKB1 levels were transcriptionally regulated. Conclusions ERα repressively modulates the expression of LKB1 at the transcriptional level. Targeting the expression of LKB1 by modulating ERα signaling may provide a potential approach to further evaluate its function in ERα-positive breast cancers. |
| Databáze: | OpenAIRE |
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