Differential Effects of Growth Factors Acting by Autocrine and Paracrine Pathways in Breast Cancer Cells

Abstract

The extent and nature of the interaction between oestrogen and insulin-like growth factors (IGFI, IGFII) in growth regulation of breast cancer cells has been extensively debated in recent years (Yee, 1992). However, one question which has received little attention concerns the relevance of the source of the IGF to breast cancer cell growth. IGFI is considered to be a paracrine regulator of breast cancer cells whilst IGFII may act by both autocrine and paracrine mechanisms (Yee, 1992). It remains a possibility that there could be different consequences to breast cancer cells when a growth factor acts by autocrine or paracrine pathways. Even in cell culture experiments, the implicit assumption seems to be that up-regulation of endogenous growth factor gene expression is synonymous with exogeneous administration of growth factor. Our recent data using a cell culture model has suggested that this assumption may not be correct and that the consequences to breast cancer cells of enhanced endogenous IGFII gene expression acting in a true autocrine loop can be different from administration of an exogenous source of IGFII.