Expression of genes involved in the regulation of p16 in psoriatic involved skin

• It has been suggested that the up-regulation of the tumour suppressor p16 gene and induction of senescence protect the phenotype of psoriatic involved skin from malignant transformation. On the other hand, Id1, which is inversely correlated with p16 has been shown to be up-regulated in psoriatic involved skin. To test the hypothesis that there may be an altered regulation of p16 in psoriatic involved skin, we have measured genes involved in the Igf-1 receptor signalling through the Ras/MAPK cascade. Igf-1R, IGFBP3, hRas, Ets2, JunB, Egr-1, Id1, MIDA1 and p16 gene expressions were measured using quantitative real-time PCR in total RNA isolated from punch biopsies from psoriatic involved (n = 9) and uninvolved skin (n = 9) and from cutaneous squamous cell cancer (SCC) involved (n = 8) and uninvolved skin (n = 8). The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin. The p16, JunB and MIDA1 genes were up-regulated in SCC involved skin compared with uninvolved skin. Our results indicate that there may be a balance between the proliferation and induction of senescence in psoriasis. This balance may vary and the psoriatic involved skin represented in this study appears to be in a proliferative state rather than senescence. Furthermore, we suggest that the noted up-regulation of JunB, which has been shown to up-regulate p16, in combination with the previously reported elevation of p16 expression in psoriatic involved skin, may indicate activation of a pathway by which JunB may protect the psoriatic plaque by inducing p16 in an event of malignant stress.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Keyword

Biopsy

Carcinoma

Squamous Cell/genetics/metabolism/pathology

Cell Aging

Cell Cycle/genetics/physiology

Cell Proliferation

Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism

Early Growth Response Protein 1/genetics/metabolism

Gene Expression Regulation

Neoplastic/genetics

Humans

Inhibitor of Differentiation Protein 1/genetics/metabolism

Insulin-Like Growth Factor Binding Protein 3/genetics/metabolism

Multivariate Analysis

Proto-Oncogene Protein c-ets-2/genetics/metabolism

Proto-Oncogene Proteins c-jun/*genetics/metabolism

Proto-Oncogene Proteins p21(ras)/genetics/metabolism

Psoriasis/*genetics/metabolism/pathology

Signal Transduction/*genetics/physiology

Skin/metabolism/pathology

Skin Neoplasms/genetics/metabolism/pathology

Up-Regulation

Publication and Content Type

ref (subject category)

art (subject category)