02 May 2003
Resistance to skin carcinogenesis in PARP-1 knockout mice due to a defective inflammatory response
D. Martin-OlivaMed Sci Monit 2003; 9(1): 39-0 :: ID: 15102
Abstract
It is well known that inflammation is a key component in the initiation and progression of epithelial cancer [1]. In a recent studies [2] we have established that the absence of PARP-1 is able to slow down tumour formation and to increase the lifespan of p53 deficient mice. We and others have shown that PARP-1 is a transcriptional co-activator of NF-kB and PARP-1 knockout as a result of a diminished release of pro-inflammatory mediators, including NO [3,4]. In the present report we have studied the susceptibility to skin carcinogenesis in mice deficient for poly(ADP-ribose) polymerase-1. In PARP-1–/– mice development of skin tumours induced by initiation with DMBA and promotion with TPA is strongly delayed, and the final number of tumour-bearing mice and total tumour number were significantly decreased in genetically deficient mice for PARP-1. The early stages of TPA promotion are characterized by keratinocyte hyperproliferation and inflammation. Nonetheless, epidermis of PARP-1–/– mice did not show increased proliferation rates. Derregulated NF-kB has been proven to be a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators, such as TNF-a. In the absence of PARP-1 NF-kB activation and induction of TNF-a did not take place during the initiation of tumour development in cell extracts from the epidermis of the carcinogen-treated area. In view of the important roles of NF-kB in tumour promotion/progression, these results suggest that inhibition of tumour development by the abolition of PARP-1 may be mediated by impairing signal transduction pathways leading to activation of NF-kB. References: 1.Correa P: Cancer Res, 1992; 52; 6735-6740 2.Conde C, Mark M, Oliver FJ et al: EMBO Journal, 2001; 20: 3535-3543 3.Oliver FJ, Ménissier de Murcia J, Nacci C et al: EMBO Journal, 1999; 18: 4446-4454 4.Hassa PO, Covic M, Hasan S et al: J Biol Chem, 2001 Dec 7; 276(49): 45588-97
Keywords: PARP-1 knockout mice, skin carcinogenesis, NF-kB, TNF-a
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
06 Mar 2024 : Clinical Research
Comparison of Outcomes between Single-Level and Double-Level Corpectomy in Thoracolumbar Reconstruction: A ...Med Sci Monit In Press; DOI: 10.12659/MSM.943797
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
10 Apr 2024 : Clinical Research
Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Dep...Med Sci Monit In Press; DOI: 10.12659/MSM.942612
06 Mar 2024 : Clinical Research
Enhanced Surgical Outcomes of Popliteal Cyst Excision: A Retrospective Study Comparing Arthroscopic Debride...Med Sci Monit In Press; DOI: 10.12659/MSM.941102
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952