P53-dependent UVB responsiveness of human keratinocytes can be altered by cultivation on cell cycle-arrested dermal fibroblasts

In cultured human keratinocytes, the tumor suppressor p53 acts as a control element in the protective response to UVB radiation and is affected by a v ariety of factors Linked to cellular adhesion and differentiation. Because keratinocytes within the epidermis are not a homogeneous population but dif fer in their proliferative capacity and differentiation status, we compared the UVB responsiveness of primary keratinocyte populations isolated from v arious skin biopsies using p53 expression as a marker for their sensitivity to UVB, Besides keratinocytes exhibiting a UVB dose- and time-dependent up regulation of p53, keratinocyte populations were detected with high p53 exp ression levels even without irradiation. Such keratinocytes did not regulat e p53 expression in response to UVB. Furthermore their p53-mediated UVB res ponse was influenced by cocultivation with human dermal fibroblasts (HDF) b ut not with cell cycle-arrested human normal keratinocytes or HaCaT keratin ocytes, When these cells were cultivated together with arrested HDF, they d id not only reveal increased p53 expression levels after UVB treatment but also a more pronounced transcriptional activation of the p53 downstream tar get gene p21, These findings indicate that the UVB response of keratinocyte s, specifically the activation of the tumor suppressor p53, is heterogeneou s and can be affected by growth conditions.