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Hepatocyte growth factor (HGF) has been recently suggested to contribute to tumorigenesis by an autocrine mechanism in fibroblast cells overexpressing its receptor, the MET/HGFR protein. Since epithelial cells represent the primary physiologic target of HGF, we investigated whether inappropriate expression of HGF by epithelial cells which normally express MET/HGFR may also contribute to tumorigenesis. We have transfected a full length rat HGF gene into three mouse epithelial cell lines, one derived from breast (MM55) and two (BNL CL.2 and NMuLi) representing liver non-parenchymal epithelial cells (NPEC). We confirmed the presence of the transfected gene by Southern blot analysis, the production of HGF protein by immunofluorescence, and the preservation of HGF biologic activity by bio-assay. In comparison to untransfected cells, all three HGF-transfected cell lines displayed high level MET/HGFR autophosphorylation and increased ability to proliferate in media containing low serum. The two HGF-transfected liver NPEC lines, but not the HGF-transfected mammary cell line, displayed loss of cell contact growth-inhibition and acquired a markedly increased ability to form colonies in soft agar. Furthermore, the NPEC HGF-transfected cell lines formed much larger tumors in nude mice than the untransfected counterparts, with extensive invasion and sporadic lung metastases. These results demonstrate that overexpression of HGF in at least some epithelial cells contribute to tumorigenesis, and furthermore suggest a possible role for the HGF-MET/HGFR system in the progression of certain epithelial tumors.
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
July 1995,
Biochemistry and molecular biology international,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
May 1994,
Cytokine,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
November 1995,
Pharmaceutical research,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
June 1998,
British journal of cancer,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
November 1993,
Oncogene,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
June 1988,
Laboratory investigation; a journal of technical methods and pathology,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
October 1999,
The American journal of physiology,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
August 1998,
The Journal of surgical research,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
June 1977,
Cancer research,
M Johnson, and
G Koukoulis, and
K Kochhar, and
C Kubo, and
T Nakamura, and
A Iyer
July 1995,
Sheng li ke xue jin zhan [Progress in physiology],
