Expression of double-stranded RNA-activated protein kinase in keratinocytes and keratinocytic neoplasia

Michiyo Kuyama1, Gen Nakanishi, Jirô Arata

  • 1Department of Dermatology, Konkô Hospital, Okayama 719-0104, Japan.

Insights

Double-stranded RNA-activated protein kinase (PKR) is constitutively expressed in normal skin keratinocytes. Loss of PKR correlates with increased cell proliferation and altered differentiation, not malignant transformation itself.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Dermatology

Background:

  • Double-stranded RNA-activated protein kinase (PKR) is an interferon-induced protein regulating protein synthesis.
  • PKR plays roles in signal transduction, differentiation, apoptosis, cell growth, and tumorigenesis.

Purpose of the Study:

  • To examine PKR expression in normal human keratinocytes (NHEK).
  • To compare PKR expression in skin lesions with proliferating cell nuclear antigen (PCNA).

Main Methods:

  • Immunohistochemistry to detect PKR protein in skin tissues.
  • Analysis of PKR mRNA levels in NHEK with and without IFNgamma treatment.
  • Immunoblot analysis to confirm PKR protein size.

Main Results:

  • PKR mRNA and 68kDa PKR protein are expressed in NHEK.
  • PKR protein is constitutively expressed in normal epidermis and mucosa, including basal cells positive for PCNA.
  • PKR expression is reduced in basal and parabasal keratinocytes in psoriatic plaques and absent in undifferentiated squamous cell carcinoma cells.

Conclusions:

  • PKR protein is constitutively expressed in normal epidermal and epithelial keratinocytes.
  • Loss of PKR is linked to increased keratinocyte proliferation and altered differentiation, rather than malignant transformation per se.

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