The
arginine vasopressin (AVP) gene is expressed in certain
cancers such as
breast cancer, where it is believed to act as an autocrine
growth factor. However, little is known about the regulation of the AVP
protein precursor (
proAVP) or AVP-mediated signaling in
breast cancer and this study was undertaken to address some of the basic issues. The cultured cell lines examined (Mcf7, Skbr3, BT474, ZR75, Mcf10a) and human
breast cancer tissue extract were found to express
proAVP mRNA. Western analysis revealed multiple forms of
proAVP protein were present in cell lysates, corresponding to those detected in human hypothalamus extracts.
Monoclonal antibodies directed against different regions of
proAVP bound to intact live Mcf7 and Skbr3 cells.
Dexamethasone increased the amount of
proAVP-associated
glycopeptide (VAG) secreted by Skbr3 cells and a combination of
dexamethasone,
IBMX and 8br-cAMP increased cellular levels of VAG. Exogenous AVP (1, 10, and 100 nM) elevated phospho-ERK1/2 levels, and increased cell proliferation was observed in the presence of 10 nM AVP. Concurrent treatment with the V1a receptor antagonist SR49059 reduced the effects of AVP on proliferation in Mcf7 cells, and abolished it in Skbr3 cells. Results here show that
proAVP components are found at the surface of Skbr3 and Mcf7 cells and are also secreted from these cells. In addition, they show that AVP promotes
cancer cell growth, apparently through a V1-type receptor-mediated pathway and subsequent ERK1/2 activation. Thus, strategies for targeting
proAVP should be examined for their effectiveness in diagnosing and treating
breast cancer.