Growth Factor Influences Rab5 Function in Breast Cancer

Cell invasion, proliferation, migration and angiogenesis are classic indicators of metastasis. Growth factors, which include epithelial growth factor (EGF), insulin growth factors I and II (IGFI and IGFII), while important for normal cellular processes, are also pro‐metastatic as they have been implicated in most if not all aspects of this phenomena. We hypothesize that cancer metastasis may be regulated by the small GTPase, Rab5, in response to IGFI. Methods: Stable cells expressing GFP‐Rab5 and its constitutive mutants were established and the Rab5 activity in response to IGFI stimulation was determined via immunoblots. We also ascertained the migratory and invasive potential of our cell lines using a Boyden chamber assay. Results: Our study has indicated that the invasive and migratory properties of breast cancer cells were abrogated in cell lines that only expressed the inactive (GDP‐bound) form of Rab 5 irrespective of growth factor stimulation. The invasive potential of breast cancer cell lines expressing the wild type and active (GTP‐bound) form of Rab 5 were noticeably greater when exposed to growth factors. In addition, we observed that Rab5 was activated in cells incubated with IGF‐I in a time and concentration dependent. Therefore, we can tentatively conclude that Rab5 activation may play an integral role in cell invasion, proliferation and migration, particularly in response to growth factor stimulus.