Role of elafin in cancer. Like SLPI, elafin has been shown to be upregulated in numerous tumour types including mouth (Xxxxxxxx et al., 1996), urothelium (Xxxxx et al., 2001), breast (Xxxxxxxxxx et al., 2000) bladder (Xxxxxxx et al., 2005), glioblastomas (Xxxxx et al., 2008) and ovarian cancers (Xxxxxx et al., 2000, Xxxxxx et al., 2010) and it was shown to be over expressed specifically in highly differentiated squamous cell carcinomas of the lung (Xxxxxxx et al., 2002), skin (Xxxxxxxx et al., 1994), and upper respiratory tract (Westin et al., 2002) (Table 1.1). However there is conflicting evidence from other tumour types where decreases in elafin expression have been observed, as in cancers of the breast (Xxxxxx et al., 2010, Xxxxx et al., 1995) and in primary samples from numerous squamous cell carcinomas (Xxxxxx et al., 2010, Xxxxxxxxxx et al., 2000). In one study of ovarian cancer, researchers found genomic gains of elafin’s chromosomal locus in various cell lines suggesting that elafin expression may provide an advantage in cellular growth. In addition, elafin expression in these cells was shown to be specifically induced by inflammatory conditions and NFϰB activation, suggesting that inflammatory conditions are conducive to elafin expression in ovarian tumour tissues (Xxxxxx et al., 2010). In addition to being upregulated in ovarian cancer, a subsequent study showed knockdown of elafin in ovarian cancer cell lines in vitro increases the sensitivity to apoptosis induced by a number of commonly used agents including cisplatin, carboplatin, cyclophosphamide and 5-fluorouracil, which is further suggestive of a potentially advantageous role in tumour growth (Xxx et al., 2012). In contrast however, elafin was shown to be transcriptionally silenced in melanoma cells. Epigenetic suppression of the Foxa2 transcription factor was responsible for regulating elafin in melanoma cell lines and this could be reversed by a DNA methylation inhibitor which subsequently induced elafin specific growth suppression and apoptosis (Xx et al., 2011). Similarly, in a separate study, over expression of elafin in melanoma cell lines induced p53 dependent apoptosis (Xx et al., 2010). Another study showed that elafin overexpression can supress breast cancer cell proliferation by halting the cells in G0-G1 phase of the cell cycle. However, in the absence of functional Rb protein elafin induces caspase3 dependent apoptosis (Xxxxxx et al., 2010). So it seems elafin can function upstream of at least two path...
