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

Abstract

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.

Melanoma and other malignant skin cancers in psoriatic patients treated with phototherapy. Role of the p16 protein in psoriasis

“…The increased p16 protein levels in psoriatic lesions have also been reported in the study of Chaturvedi et al [11]. The observed differences in the published data for the p16 gene expression could result from different localization of psoriatic lesions, various age of the plaques and individual features of patients [22].…”

“…Mark et al showed low expression of the p16 encoding gene in the psoriatic plaques as well as in normal skin [22]. Abou et al studied the effect of phototherapy on the p16 expression and found that significantly less protein in psoriatic lesions were observed before phototherapy than in controls.…”

“…It is possible that during psoriatic plaque formation an imbalance between the proliferation and induction of senescence in the keratinocytes occurs [22]. At the early stage of the formation of psoriatic plaques, the proliferating keratinocytes might not show the increased p16 expression, while the majority of the cells of the upper layer of psoriatic epidermis becomes arrested in the G1 phase in a state termed replicative senescence, induced by the overexpression of the p16 protein [22,23].…”

“…At the early stage of the formation of psoriatic plaques, the proliferating keratinocytes might not show the increased p16 expression, while the majority of the cells of the upper layer of psoriatic epidermis becomes arrested in the G1 phase in a state termed replicative senescence, induced by the overexpression of the p16 protein [22,23]. According to Abou et al, the altered expression of cell-cycle regulatory genes, including the p16, may play a significant role in the pathogenesis of hyperproliferative diseases.…”

Methylation of the p16INK4A promoter is associated with malignant behavior in abdominal extra-adrenal paragangliomas but not pheochromocytomas

“…INK4A span the exon 1a/exon 2 junction (Mark et al 2006), while the set for p14 ARF target part of exon 1b (Supplementary Table 2, N B Kiss et al: p16 methylation in malignant chromaffin tumors www.endocrinology-journals.org Fig. 1).…”