Tazarotene, a member of the new class of acetylenic retinoids, has been shown to be effective in the treatment of several hyperproliferative skin diseases, including non-melanoma skin cancer. Its effectiveness is thought to rely on the ability to activate retinoic acid receptors beta and gamma and to induce a number of downstream anti-proliferative genes. Here, we show that the p53-related gene p73 is a target of tazarotene. Indeed, tazarotene modulates the expression of the p73 gene in immortalized keratinocyte cell lines by inducing the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the anti-apoptotic and pro-proliferative Delta Np73 isoforms. This occurs at the transcriptional level through a coordinated action on P1p73 and P2p73 promoters that control the expression of TA and AN isoforms, respectively. The selective downregulation of Delta Np73 expression by small interfering RNA led to an enhancement of tazarotene-induced bax activation and apoptosis, whereas the downregulation of both TA and Delta N isoforms impairs tazarotene-mediated apoptosis. These results indicate the relevance of p73 gene products in tazarotene-induced growth inhibition and effectiveness in the treatment of skin tumors.

Papoutsaki, M., Lanza, M., Marinari, B., Nistico, S., Moretti, F., Levrero, M., et al. (2004). The p73 gene is an anti-tumoral target of the RAR beta/gamma-selective retinoid tazarotene. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 123(6), 1162-1168 [10.1111/j.0022-202X.2004.23498.x].

The p73 gene is an anti-tumoral target of the RAR beta/gamma-selective retinoid tazarotene

MARINARI, BARBARA;NISTICO', STEVEN PAUL;CHIMENTI, SERGIO;COSTANZO, ANTONIO
2004

Abstract

Tazarotene, a member of the new class of acetylenic retinoids, has been shown to be effective in the treatment of several hyperproliferative skin diseases, including non-melanoma skin cancer. Its effectiveness is thought to rely on the ability to activate retinoic acid receptors beta and gamma and to induce a number of downstream anti-proliferative genes. Here, we show that the p53-related gene p73 is a target of tazarotene. Indeed, tazarotene modulates the expression of the p73 gene in immortalized keratinocyte cell lines by inducing the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the anti-apoptotic and pro-proliferative Delta Np73 isoforms. This occurs at the transcriptional level through a coordinated action on P1p73 and P2p73 promoters that control the expression of TA and AN isoforms, respectively. The selective downregulation of Delta Np73 expression by small interfering RNA led to an enhancement of tazarotene-induced bax activation and apoptosis, whereas the downregulation of both TA and Delta N isoforms impairs tazarotene-mediated apoptosis. These results indicate the relevance of p73 gene products in tazarotene-induced growth inhibition and effectiveness in the treatment of skin tumors.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/35 - Malattie Cutanee e Veneree
English
Con Impact Factor ISI
Apoptosis; Keratinocytes; p53; p63; Skin cancer
gene product; protein Bax; protein p53; protein p73; small interfering RNA; tazarotene; apoptosis; article; cancer inhibition; cell immortalization; cell line; controlled study; down regulation; drug effect; drug efficacy; gene expression; human; human cell; keratinocyte; priority journal; skin tumor; Animals; Apoptosis; Cell Line, Transformed; DNA-Binding Proteins; Down-Regulation; Gene Expression; Genes, Tumor Suppressor; Humans; Keratinocytes; Keratolytic Agents; Mice; Nicotinic Acids; Nuclear Proteins; Receptors, Retinoic Acid; RNA, Small Interfering; Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Proteins
Papoutsaki, M., Lanza, M., Marinari, B., Nistico, S., Moretti, F., Levrero, M., et al. (2004). The p73 gene is an anti-tumoral target of the RAR beta/gamma-selective retinoid tazarotene. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 123(6), 1162-1168 [10.1111/j.0022-202X.2004.23498.x].
Papoutsaki, M; Lanza, M; Marinari, B; Nistico', Sp; Moretti, F; Levrero, M; Chimenti, S; Costanzo, A
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/49167
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact