Characterization of endogenous E2F transcriptional activities in hepatocellular, gastric and colorectal cancer cell lines

Abstract

In many human cancers, genetic alterations in E2F-pRB pathway have been frequently observed. The E2F transcription factors are known to play pivotal roles in the control of the G1/S transition of cell cycle, and their activities are highly elevated in the cells infected with a DNA tumor virus. We investigated the endogenous E2F transcriptional activities of human hepatocellular, gastric and colorectal cancer cells using a synthetic E2F-responsive reporter vector. As the result we could classify the cells into three categories according to the endogenous E2F transcriptional activity, i.e., low level or negative activity, moderate level, and high level. Cell lines such as HepG2, Hep3B, PLC/PRF/5, SNU-182, SNU-354, Colo205 and HCT116 had low to negative level of endogenous E2F transcriptional activity. On the other hand, SNU-368, SNU-387, SNU-449, SNU-484, SNU-638, SW480, SW620, DLD1 and HCT15 cells showed a moderate level, while strong E2F transcriptional activities were observed in SNU-475 and SNU-216 cells. The negative E2F activity observed in several cancer cells might be due to the active repression of universal transcription factors by the pRB-E2F complex. Thus, although several cancer cells maintained the functional status of E2Fs as the active repressors of universal transcription factors, most of the cancer cells had the repression lifted and showed a significant level of E2F-mediated transcriptional activity. These results suggest that the relief of E2F from pRB-mediated check and its subsequent activation is a general phenomenon accompanying the human carcinogenesis.