Identification and Function of Ets Target Genes Involved in Lung Cancer Progression
Abstract
Survival rates for lung cancer remain at 15%, unchanged in the past four decades. In lung cancer, increased Ets1 expression is associated with poor prognosis. We tested our hypothesis that Ets1 contributes to lung tumorigenesis by binding to specific promoters that control transcription of genes involved in EMT, such as Twist1. We used a mouse lung cancer model with metastasis driven by conditionally activated Kras and concurrent tumor suppressor Lkb1 loss (KrasG12D/Lkb1L/L model) and a similar model but one that does not metastasize, driven by conditionally activated Kras alone (KrasG12D model). We measured expression of Twist in KrasG12D /Lkb1L/L and KrasG12D cell lines. Using ChIP assays, we determined whether Ets1 binds Twist1. We determined whether silencing or overexpressing Ets1 alters Twist1 expression. Ets1 and Twist1 differ in gene expression between KrasG12D (low Ets1 and Twist1) and KrasG12D/Lkb1L/L (high Ets1 and Twist1) tumors. In human lung tumors, Twist1 and Ets1 staining positively correlate. ChIP assays confirm binding of Ets1 to Twist1 promoter. Silencing Ets1 decreases Twist1 expression; whereas overexpressing does the opposite. In mouse and human lung cancer cells, Ets1 regulates the expression of Twist1. Therapeutic targeting of EMT regulators could be useful to impair tumor metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA573588
Entities
People
- Hasmeena Kathuria
Organizations
- Boston Medical Center