The phospholipid hydrolase phospholipase C71 (PLC gamma 1) plays a major role in regulation of cell proliferation, development, and cell motility. Overexpression of PLC gamma 1 is associated with tumor development, and it is overexpressed in some tumors. Matrix metalloproteinase-3 (MMP-3) is a protein involved in tumor invasion and metastasis. Here, we demonstrate that overexpression of PLC gamma 1 stimulates MMP-3 expression at the transcriptional level via the PKC-mediated Raf/MEK1/ERK signaling cascade. We propose that modulation of PLC gamma 1 activity might be of value in controlling the activity of MMPs, which are important regulators of invasion and metastasis in malignant tumors. (c) 2006 Elsevier Inc. All rights reserved.