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恶性和非恶性皮肤疾病中端粒酶活性的检测

Detection of telomerase activity in malignant and nonmalignant skin conditions.

作者信息

Taylor R S, Ramirez R D, Ogoshi M, Chaffins M, Piatyszek M A, Shay J W

机构信息

University of Texas Southwestern Medical Center at Dallas 75235, USA.

出版信息

J Invest Dermatol. 1996 Apr;106(4):759-65. doi: 10.1111/1523-1747.ep12345811.

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.

摘要

端粒是线性染色体的末端区域,在正常体细胞中,端粒的长度会随着细胞的连续分裂而缩短。端粒酶是一种核糖核蛋白酶,可维持永生化细胞和生殖细胞中端粒的长度。虽然端粒酶存在于人类胎儿组织中,但出生后不久,除了生殖细胞、造血细胞和大多数人类原发性肿瘤外,无法检测到端粒酶活性。在本研究中,我们发现77例基底细胞癌中有73例、18例非转移性皮肤鳞状细胞癌中有15例以及7例皮肤黑色素瘤中有6例存在端粒酶活性,这与在防晒皮肤中检测到的极低水平形成对比。然而,与防晒皮肤相比,阳光损伤的皮肤、银屑病皮损皮肤以及来自毒漆性皮炎皮损的皮肤端粒酶活性水平有所升高,尽管低于肿瘤组织中检测到的水平。由于在皮肤的炎性病变中可以发现端粒酶活性,这表明端粒酶活性并不总是与恶性表型相关。此外,我们还表明端粒酶活性定位于新生儿包皮的表皮,这表明端粒酶由表皮细胞组成性表达。与未暴露皮肤相比,在暴露于阳光的皮肤中发现更高水平的端粒酶活性,这表明环境因素可能调节端粒酶活性。

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