已知多環芳香烴類化合物【包括2，3，7，8-tetrachlorodibenzo-p-dioxin (TCDD)與benzo[a]pyrene (B[a]P)等】可經由活化Aryl hydrocarbon receptor (AhR)與Aryl-hydrocarbon-receptor nuclear translocator (Arnt)，誘導許多代謝酵素基因表現，包括cytochrome P450 IA1 (CYPIA1)、Cytochrome P450 IB1 (CYPIB1)、NAD(P)H: quinone oxidoreductase 1 (NQO1)、Glutathione-S-transferases (GST)及Aldehyde dehydrogenase (ALDH)基因。近年來也有研究報導指出，AhR與Arnt mRNA表現量會隨著皮膚表皮層分化而增加，而且皮膚癌組織之AhR功能減弱。本研究之目的為探討AhR及Arnt蛋白表現與皮膚角質細胞分化及癌化之相關性。本研究發現（1）正常皮膚角質細胞及基底細胞癌細胞均有AhR與Arnt蛋白表現。（2）在皮膚細胞中，AhR表現與早期分化指標K1、K10同時表現，而AhR表現隨晚期分化指標involucrin表現增加而增加。（3）在皮膚組織中也顯示AhR與Arnt表現量隨著細胞分化程度越高而增加。（4）毛囊底部周圍組織表現大量AhR與Arnt。因此分化程度較高及毛囊周圍之皮膚角質細胞AhR與Arnt表現較高，代謝能力可能較高。基底細胞癌細胞雖然不具有晚期分化指標involucrin，但仍表現AhR與Arnt蛋白，因此應該具有代謝多環芳香烴類化合物之能力。 It has been shown that polycyclic aromatic hydrocarbon (PAHs) induce gene expression of cytochrome P450IA1 (CYPIA1), cytochrome P450 IB1 (CYPIB1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione-s-transferases (GST) and aldehyde dehydrogenase (ALDH) through activation of Ary1 hydrocarbon receptor (AhR) and Ary1 hydrocarbon receptor nuclear translocator (Arnt). The mRNA level of AhR and Arnt were increased during keratinocyte differentiation. Previous studies demonstrated that CYPIA1 induction was suppressed in chemically-induced mouse skin papillomas and squamous cell carcinomas. The objective of this study is to investigate the relationship between expression level of AhR and Arnt with differentiation and carcinogenesis. We found that (1) both normal keratinocytes and basal cell carcinoma cells expressed AhR and Arnt proteins; (2) AhR protein expression coincided with early differentiation markers, K1 and K10; (3) AhR protein expression increased when late differentiation markers, involucrin, increased. In normal skin tissues, AhR and Arnt protein expression increased in late differentated granular layers and keratinocytes around hair follicle. In conclusion, AhR and Arnt expression occur in early differentiated keratinocytes and increased in late differentiation keratinocytes. Although basal cell carcinoma cells failed to express late differentiation markers, they expressed AhR, Arnt, and early differentiation markers.
