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| Expression of TERT in early premalignant lesions and a subset of cells in normal tissues |
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| Author(s): Kolquist KA, Ellisen LW, Counter CM, Meyerson M, Tan LK, Weinberg RA, Haber DA, Gerald WL |
| Source: NATURE GENETICS Volume: 19 Issue: 2 Pages: 182-186 Published: JUN 1998 |
| Times Cited: 255 References: 30 |
| Abstract: Activation of telomerase, the enzyme that synthesizes the telomere ends of linear chromosomes, has been implicated in human cell immortalization and cancer cell pathogenesis. Enzyme activity is undetectable in most normal cells and tissues, but present in immortal cells and cancer tissues(1-3). While expression of TERC, the RNA component of telomerase, is widespread(4-6), the restricted expression pattern of TERT, the telomerase catalytic subunit gene, is correlated with telomerase activity(7-9), and its ectopic expression in telomerase-negative cells is sufficient to reconstitute telomerase activity(10-12) and extend cellular lifespan(13). We have used in situ hybridization to study TERT expression at the single-cell level in normal tissues and in various stages of tumour progression. In normal tissues, including some that are known to be telomerase-negative, TERT mRNA was present in specific subsets of cells thought to have long-term proliferative capacity. This included mitotically inactive breast lobular epithelium in addition to some actively regenerating cells such as the stratum basale of the skin. TERT expression appeared early during tumorigenesis in vivo, beginning with early pre-invasive changes in human breast and colon tissues and increasing mRNA present within individual cells and in the number of expressing cells within a neoplastic lesion. The physiological expression of TERT within normal epithelial cells that retain of tumorigenesis have implications for the regulation of telomerase expression and for the identification of cells that may be targets for malignant transformation. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gerald, WL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA |
Addresses:
1. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
2. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA
3. Harvard Univ, Sch Med, Charlestown, MA 02129 USA
4. MIT, Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA 02142 USA
5. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: ZQ468 |
| ISSN: 1061-4036 |
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