Gene Regulation and Expression Pattern of the Growth Factor Pleiotrophin in Breast Cancer

摘要

Pleiotrophin is growth factor that has mitogenic and anti-apoptotic effects in a variety of cell lines. It is also a positive regulator of tumor angiogenesis. PTN is expressed in breast cancer cell line and in primary tumor specimens as well as in fibroblasts and endothelial cell. In order to understand the biological and biochemical effects of PTN, we uncovered the PTN receptor anaplastic lymphoma kinase (ALK). Our goal was to study the signal transduction pathways for ALK/PTN axis and the modulation of ALK in stromal cells. ALK is activated by PTN and, sequentially, activates an array of second messengers in various cell lines. We identified some of the interaction partners of ALK that participate in signal transduction. In stromal cells, ALK could be upregulated by growth factors and conditioned media from an array of cancer cells. Upregulated levels of ALK in HUVEC render these cells more susceptible to PTN and promote angiogenesis. Moreover, we tested the functional consequences of downregulation of ALK by si RNA. This approach, coupled with designing small molecule inhibitors for ALK would contribute to blocking of the activation of ALK in stromal cells and promotion of tumor growth in response to PTN secreted from human mammary cancer cells.