Antipeptide antibodies to two distinct regions of amphiregulin have been developed. To date, these antibodies have been shown to be useful for immunoprecipitation of AR, immunocytochemical analysis of AR expression in cultured cells and immunohistochemical detection of AR in formalin-fixed, paraffin-embedded tissues. Studies using ovarian carcinoma cells and their normal counterparts, ovarian surface epithelial cells, revealed that (1) AR can act as both a growth inhibitor and stimulator of normal and carcinoma cells; (2) AR can be targeted to the nucleus of cells and thus may elicit a biological response there and (3) AR is localized to the nucleoli of carcinoma cells whereas it is localized throughout the nucleus of the normal cells. The role that AR plays in normal and malignant colonic epithelial cells in vitro and in vivo has also been studied. This work has shown that AR can act as an autocrine growth factor for cancer cells in vitro by acting via an extracellular autocrine loop that involves the EGF receptor. The in vivo studies indicate that AR may not only play a role as a growth regulator, but may play a role in differentiation. Future studies will focus on the following issues: (1) what is the biological consequences of AR being targeted to the nucleus of cells; (2) does the targeting of AR to the nucleus necessitate secretion of AR to the extracellular medium or can it be directly targeted to the nucleus? (3) is there a novel receptor for AR, in addition to the EGF receptor? and (4) is AR more than just a regulator of cell growth and does it play a role in biological processes such as differentiation?
