Cell cycle control and beyond: emerging roles for the retinoblastoma gene family

Abstract The Inhibitor of Growth (ING) gene family is a group of tumor suppressor genes that play important roles in cell cycle control, senescence, DNA repair, cell proliferation, and apoptosis. However, inactivation and downregulation of these proteins have been related in some neoplasms. The present study aimed to evaluate the immunohistochemical profiles of ING3 and ING4 proteins in a series of benign epithelial odontogenic lesions. Methods: The sample comprised of 20 odontogenic keratocysts (OKC), 20 ameloblastomas (AM), and 15 adenomatoid odontogenic tumors (AOT) specimens. Nuclear and cytoplasmic immunolabeling of ING3 and ING4 were semi-quantitatively evaluated in epithelial cells of the odontogenic lesions, according to the percentage of immunolabelled cells in each case. Descriptive and statistics analysis were computed, and the p-value was set at 0.05. Results: No statistically significant differences were found in cytoplasmic and nuclear ING3 immunolabeling among the studied lesions. In contrast, AOTs presented higher cytoplasmic and nuclear ING4 labeling compared to AMs (cytoplasmic p-value = 0.01; nuclear p-value < 0.001) and OKCs (nuclear p-value = 0.007). Conclusion: ING3 and ING4 protein downregulation may play an important role in the initiation and progression of more aggressive odontogenic lesions, such as AMs and OKCs.

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The Retinoblastoma Gene Family in Cell Cycle Regulation and Suppression of Tumorigenesis

Results and Problems in Cell Differentiation - Cell Cycle Regulation ◽

10.1007/400_002 ◽

2006 ◽

pp. 183-225 ◽

Cited By ~ 17

Author(s):

Jan-Hermen Dannenberg ◽

Hein P. J. te Riele

Keyword(s):

Cell Cycle ◽

Gene Family ◽

Cell Cycle Regulation ◽

Retinoblastoma Gene ◽

Cycle Regulation

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E2F-5, a new E2F family member that interacts with p130 in vivo.

Molecular and Cellular Biology ◽

10.1128/mcb.15.6.3082 ◽

1995 ◽

Vol 15 (6) ◽

pp. 3082-3089 ◽

Cited By ~ 122

Author(s):

E M Hijmans ◽

P M Voorhoeve ◽

R L Beijersbergen ◽

L J van 't Veer ◽

R Bernards

Keyword(s):

Cell Cycle ◽

Dna Binding ◽

Gene Family ◽

Binding Activity ◽

Transactivation Domain ◽

Retinoblastoma Gene ◽

Dna Binding Activity ◽

E2f Transcription Factors ◽

G0 Phase

E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and E2F-3, the repressor is the product of the retinoblastoma gene, pRb. E2f-4 interacts with pRb-related p107 and not with pRb itself. Recently, a cDNA encoding a third member of the retinoblastoma gene family, p130, was isolated. p130 also interacts with E2F DNA binding activity, primarily in the G0 phase of the cell cycle. We report here the cloning of a fifth member of the E2F gene family. The human E2F-5 cDNA encodes a 346-amino-acid protein with a predicted molecular mass of 38 kDa. E2F-5 is more closely related to E2F-4 (78% similarity) than to E2F-1 (57% similarity). E2F-5 resembles the other E2Fs in that it binds to a consensus E2F site in a cooperative fashion with DP-1. By using a specific E2F-5 antiserum, we found that under physiological conditions, E2F-5 interacts preferentially with p130.

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