| In this study, we have used a well-validated breast cancer animal model to examine the malignant progression process. We have demonstrated that disruption of Pthrp dramatically delays the initial and subsequent steps of malignant conversion of the mammary epithelial cell, without affecting the mammary gland development. PTHrP acts as a promoter of oncogenesis and metastasis upstream of a number of critical checkpoints for PyVMT, such as Akt1, Akt2, factor VIII Bcl-2 and cyclin D1, with the most interesting being CXCR4. This suggests a novel role for PTHrP as a facilitator of oncogenes and emphasizes the importance of attempting its targeting for therapeutic purposes. |
