Overexpression of hepatoma-derived growth factor in melanocytes does not lead to oncogenic transformation.
BACKGROUND
HDGF is a growth factor which is overexpressed in a wide range of tumors. Importantly, expression levels were identified as a prognostic marker in some types of cancer such as melanoma.


METHODS
To investigate the presumed oncogenic/transforming capacity of HDGF, we generated transgenic mice overexpressing HDGF in melanocytes. These mice were bred with mice heterozygous for a defective copy of the Ink4a tumor suppressor gene and were exposed to UV light to increase the risk for tumor development both genetically and physiochemically. Mice were analyzed by immunohistochemistry and Western blotting. Furthermore, primary melanocytes were isolated from different strains created.


RESULTS
Transgenic animals overexpressed HDGF in hair follicle melanocytes. Interestingly, primary melanocytes isolated from transgenic animals were not able to differentiate in vitro whereas cells isolated from wild type and HDGF-deficient animals were. Although, HDGF-/-/Ink4a+/- mice displayed an increased number of epidermoid cysts after exposure to UV light, no melanomas or premelanocytic alterations could be detected in this mouse model.


CONCLUSIONS
The results therefore provide no evidence that HDGF has a transforming capacity in tumor development. Our results in combination with previous findings point to a possible role in cell differentiation and suggest that HDGF promotes tumor progression after secondary upregulation and may represent another protein fitting into the concept of non-oncogene addiction of tumor tissue.
Institute of Biochemistry and Molecular Biology, University of Bonn, Nussallee 11, 53115 Bonn, Germany.
Angela
A
Sedlmaier
Nicolas
N
Wernert
Rainer
R
Gallitzendörfer
Mekky M
MM
Abouzied
Volkmar
V
Gieselmann
Sebastian
S
Franken
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D023061:Gene Order; D018390:Gene Targeting; D005838:Genotype; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D012867:Skin / Q000378:metabolism / Q000473:pathology
D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor