Detection of Telomerase Activity in Malignant and Nonmalignant Skin Conditions

Abstract

Telomeres are the end regions of linear chromosomes, and in normal somatic cells the lengths of telomeres shorten with successive cell divisions. Telomerase, a ribonucleoprotein enzyme, maintains the length of telomeres in immortal and germline cells. Although present in human fetal tissues, shortly after birth telomerase activity is not detectable except in germline cells, hematopoietic cells, and most human primary tumors. In the present study we show telomerase activity to be present in 73 of 77 basal cell carcinomas, 15 of 18 nonmetastatic cutaneous squamous cell carcinomas, and 6 of 7 cutaneous melanomas, contrasting with extremely low levels detected in sun-protected skin. Sun-damaged skin, psoriatic lesional skin, and skin from lesions of poison ivy dermatitis, however, have increased levels of telomerase activity compared to sun-protected skin, although less than that detected in tumor tissue. Because telomerase activity can be found in inflammatory lesions of the skin, this indicates that telomerase activity does not always correlate with the malignant phenotype. In addition, we show that telomerase activity is localized to the epidermis of newborn foreskin, which suggests that telomerase is expressed constitutively by cells in the epidermis. Finding higher levels of telomerase activity in sun-exposed skin compared to nonexposed skin suggests that environmental factors may modulate telomerase activity.

Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFβ

“…In addition, telomerase is expressed in some normal rodent organs having self-renewal properties, such as the liver, spleen, thymus, and testis, even in adult animals (Greider, 1998). This activity has also been found in activated lymphocytes, and more recently in injured and inflamed skin, fibrotic liver, hypertensive blood vessels, and injured lungs undergoing fibrosis (Tahara et al, 1995;Taylor et al, 1996;Tsujiuchi et al, 1998;Liu et al, 1999Liu et al, , 2002Nozaki et al, 2000). Induction of this activity in injured tissues suggests a potential role for telomerase in the repair and/or fibrotic process.…”

Telomerase activity in 144 brain tumours

“…Therefore, and as originally recommended (Kim et al, 1994;Piatyszek et al, 1995), the TRAP assay was performed with 27 PCR cycles. Although relative telomerase activity of some systemic cancers has been evaluated by dilution analysis (Hiyama E et al, 1995a and b;Hiyama K et al, 1995); Tahara et al, 1995) and has even been semiquantified by several investigators (Taylor et al, 1996), the telomerase activity of tumour tissues has mostly been assessed visually as being either positive or negative (Kim et al, 1994;Chadeneau et al, 1995;Langford et al, 1995;Piatyszek et al, 1995;Sommerfeld et al, 1996). To justify the visual, 'all-or-nothing' evaluation of telomerase activity, we quantified the TRAP assays of brain tumours and compared the results with visually determined positivity.…”

“…To justify the visual, 'all-or-nothing' evaluation of telomerase activity, we quantified the TRAP assays of brain tumours and compared the results with visually determined positivity. In one semiquantitative analysis of relative telomerase activity in skin cancers (Taylor et al, 1996), the telomerase activity of the specimen was normalized to that of the internal standard, used as a positive control. However, because the PCR reaction in the TRAP assay is a competitive reaction between TS primers and the internal standard, the intensity of the internal standard is not a fixed index; rather, it is inversely proportional to the intensity of specimen.…”

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

“…It has been reported that telomerase activity is activated during tumorigenesis in transgenic animals (Chadeneau et al, 1995b); Blasco et al, 1996;Broccoli et al, 1996) and is upregulated during radiation-induced malignant transformation of human cells (Pandita et al, 1996). More recently, Taylor et al (1996) and Ueda et al (1997) have found higher levels of telomerase in the sun-exposed skin compared to unexposed skin in humans indicating a possible modulation of telomerase activity by U.V. exposure.…”

“…However, the precise mechanism for the telomerase reactivation is not clearly understood. Recently telomerase activity has been detected in the skin of sun exposed individuals suggestive of the fact that UV-B-irradiation alone could trigger the telomerase activity (Taylor et al, 1996;Ueda et al, 1997). In order to determine whether primary DNA lesions produced by UV-C-irradiation could induce the telomerase activity, we have undertaken studies in immortalized Chinese hamster cells which exhibit telomerase activity.…”