Expression of multidrug-resistance (P-glycoprotein) genes in liver cancers: A molecular example of the convergence theory of hepatocarcinogenesis?

✍ Scribed by M. Tien Kuo

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 351 KB
• Volume: 7
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.2940070203

✦ Synopsis

Liver cancer has traditionally been an attractive system for studying cancer biology Most of our knowledge about hepatocellular carcinoma (HCC) has been derived from studies using experimental animals It is well known that liver tumors in rodents can be induced by many different protocols, e g , carcinogens, toxins, steroid hormones, and dietary intervention [reviewed in 1,2] Certain strains of mice can also develop liver tumors spontaneously [3] Furthermore transgenic animals exhibiting liver targeted expression of 9/40 T-antigen [41 and human hepatitis B envelope protein genes always develop HCC [5] Because these different agents have different cellular targets and modes of cytotoxicity, it is conceivable thai these different hepatocarcinogenetic protocols produce different initial events How can such a diverse spectrum of carcinogenetic programs all produce HCC7 At the ccllular level, at least three models have been proposed to address the origins of HCC (I) Abnormal differentiation model Several investigators have suggested that abnormal differentiation of hepatocytes produce foci that subsequently develop into neoplastic nodules and, ultimately, into liver cancers [6,7] (11) Stem-cell model Using several monoclonal antibodies raised against normal and premalignant liver-cell populations to characterize the phenotypic changes occurring in different experimental models of hepatocarcinogenesis, Sell and Dunsford [8,9] found that most HCCs arise from pluripotent liver stem cells, perhaps oval cells or their precursors Recently Faris and his coworkers also demonstrated that