Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism
Oliver G. Opitz, … , Hubert E. Blum, Anil K. Rustgi
Oliver G. Opitz, … , Hubert E. Blum, Anil K. Rustgi
Published September 1, 2001
Citation Information: J Clin Invest. 2001;108(5):725-732. https://doi.org/10.1172/JCI11909.
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Article

Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism

Abstract

The immortalization of human cells is a critical step in multistep carcinogenesis. Oral-esophageal carcinomas, a model system to investigate molecular mechanisms underlying squamous carcinogenesis, frequently involve cyclin D1 overexpression and inactivation of the p53 tumor suppressor. Therefore, our goal was to establish the functional role of cyclin D1 overexpression and p53 inactivation in the immortalization of primary human oral squamous epithelial cells (keratinocytes) as an important step toward malignant transformation. Cyclin D1 overexpression alone was found to induce extension of the replicative life span of normal oral keratinocytes, whereas the combination of cyclin D1 overexpression and p53 inactivation led to their immortalization. This study also demonstrates that immortalization of oral keratinocytes can be independent of telomerase activation, involving an alternative pathway of telomere maintenance (ALT).

Authors

Oliver G. Opitz, Yasir Suliman, William C. Hahn, Hideki Harada, Hubert E. Blum, Anil K. Rustgi

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Figure 2

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Cell-cycle pattern of the parental and derived oral keratinocytes. Cell-...
Cell-cycle pattern of the parental and derived oral keratinocytes. Cell-cycle analysis of OKF6, OKF6-D1, OKF6-Δp53, and OKF6-D1/Δp53 cells was done under standard conditions using FACScan. Cell-cycle analysis is displayed either as a histogram or as a table. (a) OKF6; (b) OKF6-D1; (c) OKF6-Δp53; and (d) OKF6-D1/Δp53.