Identification of constitutive expression of Glutathione S transferase P1 in human preneoplastic keratinocytes

Introduction

Glutathione S-transferase P1 (GSTP1), a member of the GST enzyme superfamily, is associated with pathogenesis of different cancers including two important skin cancers, skin squamous cell carcinoma and basal cell carcinoma. In normal skin cells, the expression of GSTP1 is regulated by transcription factor Nuclear factor erythroid related factor 2 (Nrf2) and associated Nrf2- ARE signaling pathway. Our study aimed to analyse the expression of GSTP1 of human precancerous keratinocytes (HaCaT cells) during activation of Nrf2

Materials/methods

HaCaT cells and their corresponding Nrf2-ARE luciferase reporter cells were treated by the known Nrf2 activators, ginger phenylpropanoids and quercetin, and the level of Nrf2 activity was subsequently determined. Western blot analyses were used to determine the level of GSTP1

Results and conclusions

 While both ginger phenylpropanoids and quercetin significantly increased the level of Nrf2 activity in HaCat cells, the level GSTP-1 was not changed. Such phenomenon of unresponsive downstream target expression in HaCaT cells is consistent with a constitutive expression of GSTP1. As the constitutive expression of GSTP-1 is typical to different types of cancer, its role in initial phases of neoplastic and malignant transformation of skin keratinocytes is indicated.