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Protooncogene expression in normal and psoriatic skin
J T Elder1, A Tavakkol, S B Klein
1Department of Dermatology, University of Michigan, Ann Arbor.
Abstract:
The expression of the c-myc, c-fos, c-jun, c-erbB, and c-Ha-ras protooncogenes was compared by Northern blot analysis of total RNA extracted from keratome biopsies of normal skin and psoriatic plaques. Isolation of intact RNA from frozen tissue required careful attention to technique during the early stages of extraction. Densitometric analysis revealed 1.5- to 2.5-fold elevations of c-myc transcript levels in lesional psoriatic relative to normal epidermis. Similar increases in cyclophilin and lipocortin II transcripts were also observed and may reflect characteristic differences in RNA preparations from normal and psoriatic epidermis. C-myc, c-jun, c-erbB, c-fos, and c-Ha-ras transcript levels were not significantly increased in lesional psoriatic epidermis when protooncogene mRNA levels were normalized to those of the cyclophilin or lipocortin genes. In contrast, transforming growth factor-alpha (TGF-alpha) transcripts were significantly increased (10- to 20-fold) with or without prior normalization. C-myc, c-fos, and c-jun transcripts were significantly induced over in vivo levels 2-4 h after organ culture of normal or psoriatic keratome biopsies, demonstrating that these genes can be highly expressed in the context of tissue injury. Our results suggest that overexpression of these protooncogenes per se is not central to the pathogenesis of psoriatic epidermal hyperplasia.
Insights
Protooncogene expression in psoriasis was studied. While c-myc levels were elevated in psoriatic skin, normalization revealed no significant increase, suggesting protooncogenes are not central to psoriasis pathogenesis.
Area of Science:
- Dermatology
- Molecular Biology
- Oncology
Background:
- Psoriasis is a chronic inflammatory skin condition characterized by epidermal hyperplasia.
- Protooncogenes play a role in cell growth and differentiation, and their dysregulation is implicated in various cancers.
Purpose of the Study:
- To compare the expression levels of specific protooncogenes (c-myc, c-fos, c-jun, c-erbB, c-Ha-ras) in normal skin versus psoriatic plaques.
- To investigate the role of these protooncogenes in the pathogenesis of psoriatic epidermal hyperplasia.
Main Methods:
- Northern blot analysis of total RNA extracted from normal skin and psoriatic plaque keratome biopsies.
- Densitometric analysis to quantify transcript levels.
- Normalization of protooncogene mRNA levels to housekeeping genes (cyclophilin, lipocortin II).
- Organ culture of tissue biopsies to assess gene induction after injury.
Main Results:
- Initial analysis showed 1.5- to 2.5-fold elevations of c-myc transcripts in psoriatic lesions compared to normal skin.
- After normalization to cyclophilin or lipocortin II, c-myc, c-jun, c-erbB, c-fos, and c-Ha-ras transcript levels were not significantly increased in psoriatic epidermis.
- Transforming growth factor-alpha (TGF-alpha) transcripts were significantly elevated (10- to 20-fold) in psoriatic lesions.
- C-myc, c-fos, and c-jun transcripts showed significant induction after organ culture, indicating responsiveness to tissue injury.
Conclusions:
- Overexpression of the studied protooncogenes is not a primary factor in the epidermal hyperplasia seen in psoriasis.
- TGF-alpha may play a more significant role in the pathogenesis of psoriatic skin lesions.
- Protooncogene expression can be rapidly induced by tissue injury, independent of the psoriatic condition.