Telomerase activity in melanoma and non-melanoma skin cancer.
Telomeres are specialized structures consisting of repeat arrays of TTAGGGn located at the ends of chromosomes. They are essential for chromosome stability and, in the majority of normal somatic cells, telomeres shorten with each cell division. Most immortalized cell lines and tumours reactivate telomerase to stabilize the shortening chromosomes. Telomerase activation is regarded as a central step in carcinogenesis and, here, we demonstrate telomerase activation in premalignant skin lesions and also in all forms of skin cancer. Telomerase activation in normal skin was a rare event, and among 16 samples of normal skin (one with a history of chronic sun exposure) 12.5% (2 out of 16) exhibited telomerase activity. One out of 16 (6.25%) benign proliferative lesions, including viral and seborrhoeic wart samples, had telomerase activity. In premalignant actinic keratoses and Bowen's disease, 42% (11 out of 26) of samples exhibited telomerase activity. In the basal cell carcinoma and cutaneous malignant melanoma (CMM) lesions, telomerase was activated in 77% (10 out of 13) and 69% (22 out of 32) respectively. However, only 25% (3 out of 12) of squamous cell carcinomas (SCC) had telomerase activity. With the exception of one SCC sample, telomerase activity in a positive control cell line derived from a fibrosarcoma (HT1080) was not inhibited when mixed with the telomerase-negative SCC or CMM extracts, indicating that, overall, Taq polymerase and telomerase inhibitors were not responsible for the negative results. Mean telomere hybridizing restriction fragment (TRF) analysis was performed in a number of telomerase-positive and -negative samples and, although a broad range of TRF sizes ranging from 3.6 to 17 kb was observed, a relationship between telomerase status and TRF size was not found.
Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex, UK.
C N
CN
Parris
S
S
Jezzard
A
A
Silver
R
R
MacKie
J M
JM
McGregor
R F
RF
Newbold
D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D017931:DNA Primers; D004789:Enzyme Activation; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D012867:Skin / Q000201:enzymology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D017931:DNA Primers; D019098:Telomerase