NMSC I: Epidemiology – Genetics – Clinical Aspects
Poly(ADP-ribosylation) is a major post-translational (epigenetic) modification involving a large number of proteins of eukaryotic cells. Several lines of evidence indicate that the Poly(ADP-ribosylation) of histones, beyond the well-known activity in DNA strand breaks repair, plays a pivotal role also in chromatin structure, replication and assembly [1–2].
A critical role in chromosome assembly and replication has been shown also for the Chromatin Assembly Factor (CAF)-1 complex, which expresses at high level its p60 subunit whenever a hyperproliferative condition takes place in eukaryotic cells [3–4].
We examined the immunohistochemical expression of PARP-1 and CAF-1/p60 in a selected series of squamous cell carcinomas (SCC) of the head and neck region, to evaluate its relationship with the clinical and pathological features of tumors.
The results of the study support the existence of a statistically significative correlation between the overexpression of both the proteins and the worse prognosis of patients, outlining the role of epigenetic events in the gain of aggressiveness of skin and mucosal SCC, and the role of PARP-1 and CAF-1/p60 as specific promising targets for molecular therapies for SCC.
1. Boulikas T. Poly (ADP-ribosylated) histones in chromatin replication. J Biol Chem 1990; 265:14638–14647.
2. Inbar-Rozensal D, Castiel A, Visochek L, Castel D, Dantzer F, Izraeli S, Cohen-Armon M. A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors. Breast Cancer Research 2009; 11:R78.
3. Ratnam K, Low JA. Current development of clinical inhibitors of poly(ADP-ribose) polymerase in oncology. Clin Cancer Res 2007; 13:1383–1388.
4. Staibano S, Mignogna C, Lo Muzio L, Mascolo M, Salvatore G, Di Benedetto M, et al.
Chromatin assembly factor-1 (CAF-1)-mediated regulation of cell proliferation and DNA repair: a link with the biological behaviour of squamous cell carcinoma of the tongue? Histopathology 2007; 50:911–919.