Telomerase and cell proliferation in mouse skin papillomas

Abstract

The progression of chemically induced mouse skin papillomas is paralleled by an increase in telomerase activity. In this study, we compared telomerase activity and rate of cell proliferation in papillomas obtained early versus late in papilloma progression. Eighteen early papillomas (after 15 wk of promotion) showed no evidence of telomerase activity, and their average cell proliferation index was 26.6% +/- 6.3. On the other hand, most of the papillomas harvested after 25 wk of promotion showed high levels of telomerase activity, but their average cell proliferation index (30.8% +/- 6.2) was not different from that of the early lesions. We concluded that there appears to be no association between the level of telomerase activity observed in mouse skin papillomas and the rate of cell proliferation of each individual tumor. Telomerase expression may indicate the existence of more abundant tumor subpopulations in advanced papillomas with proliferative potential for autonomous growth.

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse

“…However, a signi®cant upregulation of telomerase activity was observed in the skin at 4 weeks of UVB exposure. Higher expression of telomerase activity in UVBinduced papillomas and carcinomas observed in this study is similar to earlier studies in mouse skin papillomas and tumors induced by chemical carcinogens (Bednarek et al, 1995(Bednarek et al, , 1997. Our data showing an increase of telomerase activity during progressive stages of UVB tumorigenesis suggest that UVB exposure results in activation of telomerase and the activation occurs at an early stage of photocarcinogenesis.…”

“…However, in the normal mouse tissue including skin, the telomerase activity was not detectable (Bednarek et al, 1995). Consistent with these ®ndings, in the present study, telomerase activity was barely detectable in the epidermis of non-irradiated mouse.…”

Stratification of telomerase activity in cancer reveals associations with senescence and genomic instability

“…Cellular senescence plays a complex role in cancer, exhibiting both tumor-suppressive and tumor-promoting characteristics, and has been proposed as an emerging hallmark of cancer [73] , [74] , [75] , [76] . Although senescent cells display low proliferative potential [77] , they can escape senescence arrest and resume proliferation [78] by activating telomere maintenance mechanisms, most commonly through telomerase reactivation [79] . Given the close interplay between telomerase and senescence in tumor biology, we next examined their association across multiple cancer types.…”

Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes

“…In wild‐type mice, initiation using 7,12‐ dimethylbenz[ a ]anthracene (DMBA) and subsequent promotion with 12‐ o ‐tetradecanoylphorbol 13‐acetate (TPA) leads to papillomas that are hyperplastic, well‐differentiated, skin lesions. H‐ ras activation, loss of the p53 tumor suppressor and telomerase upregulation are reported in the majority of DMBA‐initiated papillomas (Balmain et al ., 1984, 1992; Quintanilla et al ., 1986; Bednarek et al ., 1997). Furthermore, when telomeres are critically short, as in late generation mice deficient for the RNA component of mouse telomerase, Terc (Blasco et al ., 1997; Lee et al ., 1998), the absence of telomerase activity has a dramatic inhibitory impact on skin tumorigenesis (González‐Suárez et al ., 2000), indicating that tumor formation in skin requires telomere maintenance above a threshold length.…”