Evidence of a Tumour Suppressive Function of E2F1 Gene in Human Breast Cancer

Abstract

Background: The E2F family of transcription factors are key regulators of genes involved in cell cycle progression, cell fate determination, DNA damage repair and apoptosis. E2F1 is unique in that it contributes both to the control of cellular proliferation and cellular death. Furthermore, unlike other E2Fs, E2F1 responds to various cellular stresses. This study aimed to examine the level of mRNA expression of E2F1 gene in normal and malignant breast tissue and correlate the level of expression to tumour stage. Materials and Methods: One hundred and twenty-seven breast cancer tissue and 33 normal tissues were analyzed. Levels of transcription of E2F1 were determined using real-time quantitative PCR, normalized against CK19. Levels of expression were analyzed against TNM stage, nodal involvement, tumour grade and distant metastasis. Results: The levels of E2F1 mRNA were lower in malignant tissues. They declined further with increasing TNM stage. This became statistically significant when TNM stages 3 and 4 were compared to TNM stages 1 and 2 disease (TNM1 vs. TNM3 p=0.032; TNM1 vs. TNM4 p=0.032; TNM2 vs. TNM3 p=0.019; TNM2 vs. TNM4 p=0.021). The levels of E2F1 also fell with increasing tumour grade, when comparing grade 2 and 3 with grade 1, however, the differences were not statistically significant. Conclusion: These results are highly suggestive of the role of E2F1 as a tumour suppressive gene in human breast cancer.