Authors: Zacharatos P.¹; Kotsinas A.¹; Evangelou K.¹; Karakaidos P.¹; Vassiliou L-V.¹; Rezaei N.¹; Kyroudi A.¹; Kittas C.¹; Patsouris E.²; Papavassiliou A.G.³; Gorgoulis V.G.¹

Source: The Journal of Pathology, Volume 203, Number 3, July 2004 , pp. 744-753(10)

Publisher: John Wiley & Sons, Ltd.

Abstract:

E2F-1 is a pivotal transcription factor that integrates signals from a variety of G1/S phase regulators and modulates diverse cellular functions, such as DNA synthesis, repair, mitosis, and apoptosis. Its role in cellular proliferation and apoptosis, as depicted from experimental models and limited reports in human malignancies, remains a matter of debate. Recently, in non-small cell lung cancer, it was observed that E2F-1 overexpression was associated with tumour growth, implying an ‘oncogenic’ effect. To clarify further the role of E2F-1 in carcinogenesis, the investigation was expanded in four of the most common human malignancies by examining its expression status and putative impact on tumour kinetics. These issues were addressed by immunohistochemical and molecular means in 52 breast carcinomas, 42 prostate adenocarcinomas, 58 colon adenocarcinomas, and 77 superficial bladder transitional cell carcinomas (TCCs). The following results were found: (i) in breast carcinomas, E2F-1 expression correlated with proliferation (p < 0.001) and growth index (p = 0.001); (ii) in prostate adenocarcinomas, absence of E2F-1 was noted, in contrast to its expression in normal and hyperplastic glands; (iii) in colon adenocarcinomas, E2F-1 expression was inversely related to growth index (p = 0.001), being expressed in lesions with increased apoptosis (p = 0.001) and low proliferation (p < 0.001); and (iv) in superficial TCCs, E2F-1 expression correlated with proliferation (p = 0.002). Taken together, these results suggest that E2F-1 has a growth-promoting effect in breast carcinomas and superficial TCC, whereas the opposite seems to be the case for colon and prostate cancer. To interpret the above findings, the status of the pRb and p53 tumour suppressor pathways, which are known to affect E2F-1 activity, was further investigated. The results suggest that the actions of E2F-1 are mainly dependent on the functionality of these pathways. Nevertheless, the data also imply that p53-independent pathways may play a nodal role in the function of E2F-1 in colon cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: E2F-1; proliferation; apoptosis; tumour growth; breast carcinomas; prostate carcinomas; colon carcinomas; superficial bladder transitional cell carcinomas

Document Type: Research article

DOI: http://dx.doi.org/10.1002/path.1582

Affiliations: 1: Department of Histology and Embryology, Molecular Carcinogenesis Group, School of Medicine, University of Athens, Greece 2: Department of Pathology, School of Medicine, University of Athens, Greece 3: Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece

Publication date: 2004-07-01

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