H. Schlagbauer-wadl et al., Influence of increased c-Myc expression on the growth characteristics of human melanoma, J INVES DER, 112(3), 1999, pp. 332-336
Overexpression of the proto-oncogene c-myc has been associated with neoplas
tic transformation in a variety of tumors. For human melanoma high c-myc ex
pression has been found in the vertical growth phase and higher positivity
reported in metastases than primary tumors. The principle aim of this study
was to determine, whether c-Myc expression influences the metastatic behav
ior of human melanoma in the absence of lymphocyte-mediated immune phenomen
a. The growth characteristics and tumor biology of two c-myc transfectants
of the human melanoma cell line IGR39D, expressing c-Myc 1.7 and three time
s over baseline and the respective vector control were analyzed both in vit
ro and in a severe combined immunodeficient mouse model in ville. Both c-my
c transfectants showed increased growth rates, anchorage independent growth
and directed cell movement in culture. Subcutaneously implanted IGR39D mel
anomas highly overexpressing c-Myc spontaneously formed macroscopic metasta
ses (lymph nodes and lung) in severe combined immunodeficient mice in all c
ases (n = 7 per group), whereas less prominent c-Myc overexpression caused
the development of only lung micrometastases. During the time period leadin
g to terminal disease in animals injected with c-myc transfected human mela
noma cells, melanoma development was not seen in vector controls. These fin
dings suggest that constitutive high c-Myc expression in human melanoma res
ults in a more aggressive growth behavior both in vitro and in vivo and fav
ors metastasis in severe combined immunodeficient mice by factors unrelated
to immune phenomena such as class I human leukocyte antigen downregulation
known to be associated with c-Myc expression.