Multiple Genetic Alterations and Abnormal Growth Factor Network in Human Esophageal Carcinomas

Abstract

Esophageal carcinoma is the most malignant gastrointestinal neoplasm. Multiple genetic alterations of oncogenes and tumor suppressor genes take place in esophageal squamous cell carcinomas. Co-amplification of cyclin D1, hst-1, and int-2 gene is found in 40% of the primary tumors and almost all metastatic tumors. The prognosis of the patient with gene amplification is evidently poorer than those without amplification. Multiple alterations of tumor suppressor genes and negative cell cycle regulators, including p.53 gene, Rb gene, BRCA1 gene, p16 (MTS1), p15 (MTS2), and p21 (WAF1/CIP1), play an important role in the development and progression of esophageal carcinomas. Furthermore, multiple growth factor—receptor loops exist and participate in the autocrine growth of the esophageal cancer. They include epidermal growth factor (EGF), transforming growth factors (TGF) a and β, and platelet-derived growth factor (PDGF). Overexpression of EGF, TGF-α, and EGFR is closely correlated with the malignant behavior of tumor cells and patient prognosis. These growth factors stimulate production of the interstitial degradation enzymes and down-regulation of Ecadherin function, which may lead to cell invasion and metastasis.