# Distinct Regulation of the ARF and TAp73 Tumor Suppressor Genes by the Transcription Factor E2F1 Enables Discrimination of Cancer Cells from Normal Growing Cells

## TL;DR

This study shows that cancer cells can be distinguished from normal cells based on unique activity of the E2F1 protein, which activates tumor suppressor genes only in cancer cells.

## Contribution

The study identifies a unique E2F1 activity in cancer cells that activates tumor suppressor genes, enabling discrimination from normal cells.

## Key findings

- Distinct E2F1 activity activates tumor suppressor genes ARF and TAp73 in cancer cells but not in normal cells.
- Reporter assays confirmed that all 33 cancer cell lines tested have this unique E2F1 activity.
- Normal cell lines lack this distinct E2F1 activity, suggesting it is a unique feature of cancer cells.

## Abstract

Discrimination of cancer cells from normal growing cells is crucial to specifically target cancer cells. The transcription factor E2F1 is the principal target of the tumor suppressor pRB. E2F1 activated by growth stimulation activates cell cycle-related genes and facilitates cell proliferation. E2F1 activated by loss of pRB control, such as forced inactivation of pRB, activates tumor suppressor genes such as ARF and TAp73 and induces apoptosis. We show here that these genes are specifically activated by exogenously expressed E2F1 or forced inactivation of pRB but not by growth stimulation in epithelial cells. This observation indicates that E2F1 activity induced by forced inactivation of pRB contains distinct E2F1 activity that activates these tumor suppressor genes. Cancer cells survive with concomitant dysfunction of apoptosis-inducing pathways, suggesting the presence of distinct E2F1 activity specifically in cancer cells. We determined the presence of distinct E2F1 activity using E2F responsive elements of the ARF and TAp73 genes by reporter assay. All 33 cancer cell lines tested possessed distinct E2F1 activity, but five normal growing cell lines did not. These results indicate that distinct E2F1 activity is a unique characteristic of cancer cells that facilitates discrimination from normal growing cells to specifically target cancer cells.