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Upregulation of E2F transcription factors in chemically induced mouse skin tumors
S Balasubramanian1, N Ahmad, H Mukhtar
1Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract:
E2F family of transcription factors plays an important role in cell cycle regulation, oncogenesis and differentiation. E2Fs are a family of heterodimeric transcription factors composed of E2F-like and DP-like subunits. They regulate expression of specific genes controlling cellular proliferation by binding to specific sequences within the promoter regions of these target genes and affecting their transcription in a cell cycle dependent manner. Recent studies have suggested an essential role of Rb/E2F pathway in the passage of cells through the G1 phase of the cell cycle. To better understand the role of these transcription factors in epithelial tumorigenesis, we compared the expression of various proteins involved in the Rb/E2F pathway in epidermis and 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA) promoted papillomas on SENCAR mouse skin. Western blot analysis data showed 3.0- to 7.6-fold upregulation of E2F-1, E2F-2, E2F-3, E2F-4 and E2F-5 in tumors compared to normal epidermis. In tumors, the protein expression of DP-1 did not show significant change whereas that of DP-2 showed a 2.2-fold increase. Compared to normal epidermis, a significant upregulation of pRb (6.3-fold) and p107 (13-fold) was also observed in tumors. The protein expression of p130 was not detectable either in normal epidermis or in tumors. These data suggest that the overexpression of E2F proteins may be involved in the G1-S phase dysregulation that occurs during mouse skin tumorigenesis.
Insights
Overexpression of E2F transcription factors and related proteins like pRb and p107 is observed in mouse skin tumors. This suggests their involvement in cell cycle dysregulation during epithelial tumorigenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Cycle Regulation
Background:
- E2F transcription factors are crucial for cell cycle regulation, oncogenesis, and differentiation.
- The Retinoblastoma (Rb)/E2F pathway is essential for cell cycle progression through the G1 phase.
Purpose of the Study:
- To investigate the role of E2F pathway proteins in epithelial tumorigenesis.
- To compare protein expression in normal epidermis versus chemically induced mouse skin tumors.
Main Methods:
- Western blot analysis was used to quantify protein levels.
- Expression of E2F family members (E2F-1 to E2F-5), DP subunits (DP-1, DP-2), and Rb family proteins (pRb, p107, p130) was assessed.
Main Results:
- Significant upregulation of E2F-1, E2F-2, E2F-3, E2F-4, and E2F-5 (3.0-7.6 fold) was observed in tumors compared to normal epidermis.
- DP-2 expression increased 2.2-fold in tumors, while DP-1 showed no significant change.
- pRb (6.3-fold) and p107 (13-fold) were significantly upregulated in tumors; p130 was undetectable.
Conclusions:
- Overexpression of E2F proteins and associated regulatory proteins (pRb, p107) is implicated in mouse skin tumorigenesis.
- These findings suggest a role for E2F overexpression in G1-S phase dysregulation during tumor development.