Gene Modulation Accompanying Differentiation of Normal versus Malignant Keratinocytes

121

137

Section: Effect Of Mek1 Inhibitor On An Extract-induced Cox-2 Proteinmentioning

confidence: 60%

Section: Effect Of Mek1 Inhibitor On An Extract-induced Cox-2 Proteinmentioning

confidence: 99%

The Induction of Prostaglandin E2 Production, Interleukin-6 Production, Cell Cycle Arrest, and Cytotoxicity in Primary Oral Keratinocytes and KB Cancer Cells by Areca Nut Ingredients Is Differentially Regulated by MEK/ERK Activation

Chang

Lee

et al. 2004

121

137

“…PKC and Calcium Regulate hINV Gene Expression-Previous studies (29,60,61) suggest that calcium regulates hINV gene expression at the mRNA and protein level and suggest that novel PKC isoforms mediate the phorbol ester-dependent increase in hINV gene expression. The PKC regulation is transmitted via a pathway that includes novel PKC, Ras, MEKK1, MEK3, and p38 MAPK (28,29).…”

Section: Discussionmentioning

confidence: 99%

Calcium-dependent Involucrin Expression Is Inversely Regulated by Protein Kinase C (PKC)α and PKCδ

Deucher¹,

Efimova²,

Eckert³

2002

Calcium is an important physiologic regulator of keratinocyte function that may regulate keratinocyte differentiation via modulation of protein kinase C (PKC) activity. PKC␣ and PKC␦ are two PKC isoforms that are expressed at high levels in keratinocytes. In the present study,weexaminetheeffectofPKC␦andPKC␣oncalcium-dependent keratinocyte differentiation as measured by effects on involucrin (hINV) gene expression. Our studies indicate that calcium increases hINV promoter activity and endogenous hINV gene expression. This response requires PKC␦, as evidenced by the observation that treatment with dominant-negative PKC␦ inhibits calcium-dependent hINV promoter activity, whereas wild type PKC␦ increases activity. PKC␣, in contrast, inhibits calcium-dependent hINV promoter activation, a finding that is consistent with the ability of dominantnegative PKC␣ and the PKC␣ inhibitor, Go6976, to increase hINV gene expression. The calcium-dependent regulatory response is mediated by an AP1 transcription factor-binding site located within the hINV promoter distal regulatory region that is also required for PKC␦-dependent regulation; moreover, both calcium and PKC␦ produce similar, but not identical, changes in AP1 factor expression. A key question is whether calcium directly influences PKC isoform function. Our studies show that calcium does not regulate PKC␣ or ␦ levels or cause a marked redistribution to membranes. However, tyrosine phosphorylation of PKC␦ is markedly increased following calcium treatment. These findings suggest that PKC␣ and PKC␦ are required for, and modulate, calcium-dependent keratinocyte differentiation in opposing directions.

“…Keratinocytes were established from neonatal foreskin or adult skin as described (20,21). For experimental use, first subcultures of the primary keratinocyte cultures were used.…”

Section: Methodsmentioning

confidence: 99%

Bone Morphogenetic Protein-4, a Novel Modulator of Melanogenesis

Yaar¹,

Wu²,

Park

et al. 2006

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-␤ family, signal in many cells including neural precursors. Two receptors, types 1 and 2, coordinately mediate BMP signaling, and type 1 receptor has two forms: A and B. Using RT-PCR we found that neural crest-derived human melanocytes express BMP receptor-1A, -1B, and -2. Furthermore, melanocytes and the surrounding keratinocytes express BMP-4, suggesting both autocrine and paracrine effects of this molecule. Moreover, BMP-4 supplementation of cultured human melanocytes decreases melanin synthesis, tyrosinase mRNA, and protein. The mechanism of this BMP-4 effect on tyrosinase and ultimately on melanogenesis involves modest decreases of tyrosinase transcription rate and mRNA stability. Moreover, ultraviolet irradiation, the best recognized environmental stimulator of melanogenesis, down-regulated the mRNA of BMP receptor-1B in melanocytes. Our data provide evidence of a novel regulatory pathway for melanogenesis in human skin.