Calpain, also named CAPN (for
calcium-activated neutral protease), is a ubiquitous intracellular cytoplasmic non-lysosomal
cysteine endopeptidase that requires
calcium ions to exert its activity. Two major
isoenzymes are known- micro -
calpain (CAPN1) and
m-calpain (CAPN2)-requiring micromolar and millimolar
calcium concentrations for activation, respectively. Many known substrates of the different
calpain isoenzymes, such as the
transcription factors c-Fos and c-Jun, the tumour suppressor
protein p53,
protein kinase C, pp60src, or the adhesion molecule
integrin, have been implicated in the pathogenesis of various
malignancies including squamous (SCC) and basal (BCC) cell
carcinomas of human skin, suggesting an important role of the
calpain isoenzymes in malignant diseases. We have analysed the expression of
CAP1 and CAPN2
protein and
mRNA expression in BCCs and SCCs of human skin. Interestingly, CAPN1 immunoreactivity (
streptavidin-
peroxidase technique) was markedly reduced in BCCs compared to normal human skin or SCCs, while in contrast CAPN1
mRNA levels (determined by real-time PCR) were markedly elevated in BCCs and SCCs compared to normal human skin. No differences were found analysing CAPN2
protein and
mRNA expression in normal human skin, BCCs and SCCs. In conclusion, we have demonstrated for the first time alterations in
calpain mRNA expression and
protein content in malignant skin tumours that may be of importance for the
tumorigenesis and growth characteristics of BCCs and SCCs. However, our results do not allow conclusions on the function of CAPN1 and CAPN2 in BCCs and SCCs. It is not known if the CAPN genes in BCCs or SCCs exhibit functionally inactivating mutations or whether decreased CAPN1
protein expression in BCCs and elevated CAPN1
mRNA in BCCs and SCCs reflect a feedback loop coupled with increased degradation or proteolysis of CAPN1
protein.