Action of Phorbol Esters, Bryostatins, and Retinoic Acid on Cholesterol Sulfate Synthesis: Relation to the Multistep Process of Differentiation in Human Epidermal Keratinocytes

Jetten, Anton M.; George, Margaret; Pettit, George R.; Herald, Cherry L.; Rearick, James I.

doi:10.1111/1523-1747.ep12277374

Cited by 51 publications

(34 citation statements)

References 49 publications

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“…Consistent with this idea, overexpression of PKC isozymes has recently been shown to regulate TPA-responsive promoters in an isozymespeci®c manner (Reifel-Miller et al, 1996). The expression pattern of PKCZ in vivo suggests a function for this isozyme in the ®nal stages of epidermal di erentiation and corni®cation Osada et al, 1993), aspects of keratinocyte di erentiation that are also induced by TPA (Lichti and Yuspa, 1988;Yuspa et al, 1982;Jetten et al, 1989). Whether the di erences in the regulation of the ®laggrin promoter in calcium and TPA treated cells results from di erential activation of PKC isozymes remains to be determined.…”

Section: Discussionmentioning

confidence: 87%

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Rutberg

Sáez

et al. 1997

Oncogene

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The major di erentiation products of maturing keratinocytes contain AP-1 regulatory motifs, and AP-1 DNA binding activity increases in cultured keratinocytes induced to di erentiate by calcium. Here, we have analysed AP-1 transcriptional activity in mouse keratinocytes treated with calcium and 12-O-tetradecanoyl phorbol-13-acetate (TPA), two agents that induce terminal di erentiation of keratinocytes with di erent phenotypic consequences. Reporter constructs representing multimers of AP-1 sequences found in keratinocyte marker genes demonstrated that the calcium-induced AP-1 DNA binding activity does not correlate with transcriptional activation. Moreover, expression from active subunits of the pro®laggrin and spr 1 promoters increased in calcium-treated keratinocytes when the AP-1 sites were disrupted, indicating that AP-1 may negatively regulate certain promoters in these cells. In contrast, AP-1 reporter activity was increased in keratinocytes treated with TPA. This induction was dependent upon the expression of c-Fos since AP-1 transcriptional activity was not increased in TPA-treated keratinocytes derived from c-fos null mice. Analysis of AP-1 protein expression in calcium-and TPA-treated keratinocytes demonstrated that only TPA increased the expression of c-Jun, while Jun B and Jun D were induced by both of these agents. c-Fos was expressed only in TPA treated keratinocytes, Fra-2 was expressed only in calcium-treated cells, and Fra-1 was expressed in both. Exogenous expression of Fra-2 repressed AP-1 transcriptional activity in TPA-treated keratinocytes, while c-Fos expression activated the AP-1 sequence in calcium-treated keratinocytes. These data indicate that Fra-2 and c-Fos play opposing roles in regulating AP-1 activity in keratinocytes and that multiple inducerdependent regulatory pathways may exist for the expression of keratinocyte di erentiation markers.

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Section: Discussionmentioning

confidence: 87%

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Rutberg

Sáez

et al. 1997

Oncogene

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“…Previous studies have demonstrated that retinoids inhibit CS production as well as the expected increase in CSTase activity that accompanies keratinocyte differentiation (18,19). This is not surprising because it is well recognized that activation of RAR inhibits keratinocyte differentiation (51).…”

Section: Discussionmentioning

confidence: 89%

“…Interestingly, CS levels increase dramatically when rabbit tracheal epithelial cells undergo squamous differentiation, owing to a 20-to 30-fold increase in CSTase activity in the absence of retinoic acid, and CS levels decline by Ͼ 25-fold in the presence of exogenous retinoic acid (17). Similar phenomena occur in cultured human keratinocytes (CHKs) treated with retinoic acid (18,19). Retinoic acid is a natural ligand of the type 2 nuclear hormone receptor retinoic acid receptor (RAR), and activation of RAR affects many important cellular processes, such as proliferation and differentiation (20).…”

mentioning

confidence: 81%

LXR and PPAR activators stimulate cholesterol sulfotransferase type 2 isoform 1b in human keratinocytes

Jiang

Kim

Elias

et al. 2005

Journal of Lipid Research

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“…Overexpression of E2F-1 inhibits the induction of differentiation markers in normal human keratinocytes treated with differentiation-inducing agents Treatment of primary human keratinocytes cultures with TPA activates protein kinase C and induces di erentiation (Adams and Watt, 1988;Jetten et al, 1989;Saunders et al, 1993a). The early phase of keratinocyte di erentiation is characterized by the growth arrest of the cells and down regulation of proliferation-associated genes such as E2F-1 and cdc2 (Sharpe et al, 1994;Jones et al, 1997b;Saunders et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes

et al. 2000

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Squamous di erentiation of keratinocytes is associated with decreases in E2F-1 mRNA expression and E2F activity, and these processes are disrupted in squamous cell carcinoma cell lines. We now show that E2F-1 mRNA expression is increased in primary squamous cell carcinomas of the skin relative to normal epidermis. To explore the relationship between E2F-1 and squamous di erentiation further, we examined the e ect of altering E2F activity in primary human keratinocytes induced to di erentiate. Promoter activity for the proliferationassociated genes, cdc2 and keratin 14, are inhibited during squamous di erentiation. This inhibition can be inhibited by overexpression of E2F-1 in keratinocytes. Overexpression of E2F-1 also suppressed the expression of di erentiation markers (transglutaminase type 1 and keratin 10) in di erentiated keratinocytes. Blocking E2F activity by transfecting proliferating keratinocytes with dominant negative E2F-1 constructs inhibited the expression of cdc2 and E2F-1, but did not induce di erentiation. Furthermore, expression of the dominant negative construct in epithelial carcinoma cell lines and normal keratinocytes decreased expression from the cdc2 promoter. These data indicate that E2F-1 promotes keratinocyte proliferation-speci®c marker genes and suppresses squamous di erentiation-speci®c marker genes. Moreover, these data indicate that targeted disruption of E2F-1 activity may have therapeutic potential for the treatment of squamous carcinomas.

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Action of Phorbol Esters, Bryostatins, and Retinoic Acid on Cholesterol Sulfate Synthesis: Relation to the Multistep Process of Differentiation in Human Epidermal Keratinocytes

Cited by 51 publications

References 49 publications

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

LXR and PPAR activators stimulate cholesterol sulfotransferase type 2 isoform 1b in human keratinocytes

E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes

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