title: Keratinocyte growth factor stimulates growth of MIA PaCa-2 cells through extracellular signal-regulated kinase phosphorylation.
abstract: Keratinocyte growth factor (KGF), also known as fibroblast growth factor-7, is mainly synthesized by mesenchymal cells. KGF modulates proliferation, differentiation, migration and adhesion to extracellular matrices of epithelial cells that specifically express the KGF receptor (KGFR). We previously reported that KGF is expressed in cancer cells and adjacent stromal fibroblasts in human pancreatic cancer tissues. Furthermore, KGF is thought to stimulate the growth of certain pancreatic cancer cell lines. The aim of the present study was to examine whether the mitogen-activated protein kinase (MAPK) pathway contributes to exogenous KGF-induced pancreatic cancer cell growth. Recombinant human KGF (rhKGF) was administered to MIA PaCa-2 cells, which expressed KGFR and negligible levels of KGF. Cell growth rates in MIA PaCa-2 cells were significantly increased in a dose-dependent manner following the addition of rhKGF. In the MAPK pathway, phosphorylation of extracellular signal-regulated kinase (ERK) in MIA PaCa-2 cells was increased in a dose-dependent manner, and phosphorylation of p38 was slightly increased following the administration of 100 ng/ml rhKGF. In contrast, JNK was not phosphorylated following the addition of rhKGF in MIA PaCa-2 cells. U0126, a specific inhibitor of ERK activation, decreased the rhKGF-induced phosphorylation of ERK and the growth rates of MIA PaCa-2 cells. These findings indicated that phosphorylation of the ERK signaling pathway plays a significant role in exogenous KGF-induced pancreatic cancer cell growth.
authors: Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan.
authors: Tetsushi
authors: T
authors: Yamamoto
authors: Yoko
authors: Y
authors: Matsuda
authors: Kiyoko
authors: K
authors: Kawahara
authors: Zenya
authors: Z
authors: Naito
authors: Toshiyuki
authors: T
authors: Ishiwata