PMID- 16469527
OWN - NLM
STAT- MEDLINE
DCOM- 20070419
LR  - 20161124
IS  - 1368-8375 (Print)
IS  - 1368-8375 (Linking)
VI  - 42
IP  - 6
DP  - 2006 Jul
TI  - Hypoxia enhances c-Met/HGF receptor expression and signaling by activating 
      HIF-1alpha in human salivary gland cancer cells.
PG  - 593-8
AB  - Hypoxia increases the invasive and metastatic potential of tumor cells. Increased 
      expression of c-Met/hepatocyte growth factor (HGF)-receptor protein in response 
      to hypoxia in thyroid papillary carcinomas is hypoxia-inducible factor-1 (HIF-1) 
      dependent. Both HGF and c-Met are expressed in human salivary gland cancers. In 
      the current study, we tested whether c-Met expression was regulated by hypoxia 
      and HIF-1alpha using two human salivary gland cancer cell lines: GFP-ACC2 and 
      GFP-ACCM. Hypoxia enhanced the expression of HIF-1alpha in both cell lines, 
      whereas c-Met was markedly induced only in the GFP-ACCM cells, which have 
      metastatic potential. In the latter, hypoxia also promoted HGF-induced 
      invasiveness. Synthetic small-interfering RNA specific for HIF-1alpha inhibited 
      HIF-1alpha expression in the GFP-ACCM cells, and also suppressed the increase in 
      c-Met expression and HGF-induced invasiveness under hypoxic conditions. These 
      results suggest that hypoxia activates the HGF/c-Met system via HIF-1alpha in 
      human salivary gland cancers and might be involved in their metastasis.
FAU - Hara, Shingo
AU  - Hara S
AD  - Department of Oral and Maxillofacial Surgery, Ehime University School of 
      Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
FAU - Nakashiro, Koh-Ichi
AU  - Nakashiro K
FAU - Klosek, Sebastian K
AU  - Klosek SK
FAU - Ishikawa, Tohru
AU  - Ishikawa T
FAU - Shintani, Satoru
AU  - Shintani S
FAU - Hamakawa, Hiroyuki
AU  - Hamakawa H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060215
PL  - England
TA  - Oral Oncol
JT  - Oral oncology
JID - 9709118
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Cell Hypoxia
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Salivary Gland Neoplasms/*metabolism/pathology
MH  - Von Hippel-Lindau Tumor Suppressor Protein/metabolism
EDAT- 2006/02/14 09:00
MHDA- 2007/04/20 09:00
CRDT- 2006/02/14 09:00
PHST- 2005/10/03 00:00 [received]
PHST- 2005/10/20 00:00 [accepted]
PHST- 2006/02/14 09:00 [pubmed]
PHST- 2007/04/20 09:00 [medline]
PHST- 2006/02/14 09:00 [entrez]
AID - S1368-8375(05)00300-3 [pii]
AID - 10.1016/j.oraloncology.2005.10.016 [doi]
PST - ppublish
SO  - Oral Oncol. 2006 Jul;42(6):593-8. doi: 10.1016/j.oraloncology.2005.10.016. Epub 
      2006 Feb 15.