Bovine hepatocyte growth factor and its receptor c-Met: cDNA cloning and expression analysis in the mammary gland.

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine that plays a crucial role in the embryonic and postnatal development of various organs including the mammary gland. We cloned bovine HGF and its c-Met receptor cDNAs, and examined their expression during mammary gland development in dairy cows. The 2.5-kbp HGF cDNA clone contained a 2190 bp open reading frame coding a 730 amino acid protein, while the 4.8-kbp c-Met cDNA clone contained a 4152 bp open reading frame coding a 1384 amino acid protein. The bovine HGF and c-Met sequences exhibited more than 87% identity with those of other mammals. RT-PCR analysis revealed ubiquitous expression of both HGF and c-Met mRNAs in various bovine tissues tested. HGF mRNA was detected only in the inactive stage of bovine mammary gland development and not in the developing, lactating, and involuting stages, while c-Met mRNA was detected in the inactive and involuting stages. Immunohistochemical analysis demonstrated that the c-Met protein was found on mammary epithelial cells in the inactive, developing, and involuting stages, and on myoepithelial cells in all stages. These results suggest pivotal roles of HGF and c-Met in the development of bovine mammary gland.