Biomarkers and transcription levels of cancer-related genes in cockles Cerastoderma edule from Galicia (NW Spain) with disseminated neoplasia

Neoplastic diseases of marine bivalves

“…In the case of the softshell clam M. arenaria, high levels of p53, p63/73 and mortalin may be used as markers of DN (Siah et al, 2008a;Muttray et al, 2012). Ruiz et al (2013b) also detected higher levels of p53 in cockles C. edule affected by heavy DN than in healthy cockles.…”

“…RAS homologous genes have been characterized in some mollusk species. The sequence of the M. edulis RAS cDNA is highly conserved in regions of functional importance, including mutational hot spots (Ciocan and Rotchell, 2005); M. trossulus RAS sequence is very similar to that of M. edulis (Ciocan et al, 2006), and the sequence of C. edule has 94% identity with that of Crassostrea angulata and 93% with those of M. galloprovincialis and M. edulis (Ruiz et al, 2013b). Ciocan et al (2006) detected RAS gene over-expression in DN-affected mussels M. trossulus (all heavily affected) compared to non-affected ones; the authors found high polymorphism in the sequence of RAS gene of DN-affected mussels, much higher than in M. edulis (the latter species is less susceptible to DN).…”

“…Over-expression of some proto-oncogenes could also be used as marker for DN, such as Ras gene for mussels M. trossulus (Ciocan et al, 2006) and cockles C. edule (Ruiz et al, 2013b) and c-myc gene for softshell clams M. arenaria (Siah et al, 2012a). Recently, Arriagada et al (2014) have identified and characterized a novel retrotransposon named Steamer with an expression strongly associated with DN in M. arenaria, which constitutes a new molecular marker of the disease in softshell clams.…”

“…The level of expression of p53 family was also addressed; differential expression was detected between DN-affected clams M. arenaria (Kelley et al, 2001;Stephens et al, 2001) and DN-affected mussels M. edulis (St-Jean et al, 2005) compared to healthy controls, using antibodies to p53 family proteins. Regarding mRNA levels, Siah et al (2008a) found a higher level of expression of p53 and p73 in clams M. arenaria with moderate DN than in those with heavy, light or null DN; Muttray et al (2012) reported that p53 and p63/73 were over-expressed in hemolymph cells of clams M. arenaria with heavy DN heavy compared to clams with light or null DN; Ruiz et al (2013b) detected higher levels of p53 in the digestive gland of cockles C. edule with moderate DN than in those with heavy, light or null DN. Muttray et al (2007) characterized the mRNA of different isoforms of the p53 family in mussels M. edulis and M. trossulus; p53 and the isoform termed DNp63/p73-like, because of the similarity with DNp73 of mammals, were over-expressed in hemolymph cells from DN-affected mussels M. trossulus compared to non-affected mussels (Muttray et al, 2008); interestingly, over-expression of DNp73 serves as marker for human cancers (Di et al, 2013); furthermore, correlations in mRNA levels of the isoforms in the non-affected mussels were lost in DN-affected mussels.…”

“…The tumor-suppressor protein p53 regulates genes involved in progression through the cell cycle, DNA repair, senescence or apoptosis in response to cell stress; thus dysregulation or dysfunction of p53 can result in uncontrolled cellular proliferation; inactivation of p53 occurs in almost all cancers (Oren, 2003). A p53-like gene has been characterized in a number of mollusk species, including M. arenaria (Barker et al, 1997;Kelley et al, 2001), Spisula solidissima (Cox et al, 2003), M. edulis (Ciocan and Rotchell, 2005;Muttray et al, 2007), M. trossulus (Ciocan et al, 2006;Muttray et al, 2007), M. galloprovincialis (Stifanic et al, 2009), and C. edule (Ruiz et al, 2013b). The structure and phylogeny of p53 family in mollusks was reviewed by Walker et al (2011); various isoforms have been detected, all seem to derive from the same gene through different splicing or other transformations.…”