In vitro transformation models: modeling human cancer.

The development of cancer in humans involves a complex accumulation of genetic and epigenetic events mainly in proto-oncogenes and tumor-suppressor genes. Different combinations of these alterations have been observed in a given human cancer and an ever-increasing number of these genes seem to be involved in the distinct steps of neoplastic transformation. Nevertheless, recent successes in experimental models of immortalization and malignant transformation of human cells indicate that the disruption of a limited number of cellular pathways is sufficient to induce a cancerous phenotype in a wide variety of normal cells.

Creating oral squamous cancer cells: a cellular model of oral-esophageal carcinogenesis.

Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently found in the corresponding human cancer would significantly enhance our understanding of tumor development. Alterations in several key intracellular regulatory pathways (the pRB, p53, and mitogenic signaling pathways and the telomere maintenance system) appear to be sufficient for the neoplastic transformation of normal human cells.

Differential transcriptional regulation of human telomerase in a cellular model representing important genetic alterations in esophageal squamous carcinogenesis.

Telomerase activity is observed in approximately 90% of human cancer including esophageal squamous cell cancer. Normal somatic cells do not display telomerase activity on a regular basis. The major mechanism to regulate telomerase activity in human cells is the transcriptional control of the catalytic subunit, the human reverse transcriptase gene hTERT.