Increased expression of apoptotic markers in melanoma.
Extensive labelling for the apoptotic markers calcium channel receptor P2X(7) and caspase-3 and telomerase activity was co-localized at a similar intensity in areas affected by superficial spreading melanoma obtained from 80 patients. Labelling for each of these markers also extended 2 microm from the melanoma into the keratinocyte layer of the adjacent normal epidermis. Conversely, the calcium-regulating receptors P2X(1-3) and P2Y(2) (found in normal but not neoplastic skin) were fully de-expressed within 2 microm of the melanoma but fully expressed beyond that distance. The cell adhesion protein E-cadherin (also only present in normal skin) was progressively de-expressed from a point 2 microm from the melanoma until full de-expression within the lesion. These results show that telomerase-induced proliferation and defensive apoptosis are co-localized and simultaneous processes in melanoma tissue. Melanoma cell proliferation appears to overwhelm the apoptotic defence, perhaps due to the anti-apoptotic effects of telomerase. In addition, keratinocyte regulation of the epidermis and dermis is severely compromised by the loss of E-cadherin and P2X(1-3) and P2Y(2) receptors, resulting in a lesion that is aggressive and malignant.
Slater
Michael
M
Institute for Biomedical Research, Department of Anatomy and Histology, The University of Sydney, Sydney, NSW 2006, Australia. michaels@anatomy.usyd.edu.au
Scolyer
Richard A
RA
Gidley-Baird
Angus
A
Thompson
John F
JF
Barden
Julian A
JA
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002448:Cell Adhesion; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D020405:Dermis / Q000378:metabolism; D004792:Enzyme Precursors / Q000096:biosynthesis; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*; D058486:Receptors, Purinergic P2X7; D019098:Telomerase / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors
D014408:Biomarkers, Tumor; D015820:Cadherins; D004792:Enzyme Precursors; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D019098:Telomerase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases