| Abstract |
The crucial characteristic of malignant tumors is their ability to
metastasize. At the molecular level, many different genes and gene
products are involved in the regulation of metastasis. One of these genes
is nm23, originally described in malignant melanoma cells as a metastasis
inhibitor and different isoforms exist. It was shown that both for nm23-H1
and nm23-H2 mutations in human tumors can occur. So far very little was
known about the function of nm23-H1 and nm23-H2 in human renal cell
carcinoma and human epithelioid sarcoma and mutational analyzes of both
genes in these tumors had not been carried out. The aim of the present
work was to investigate human renal cell carcinoma and epithelioid
sarcomas on expression and the existence of mutations of genes nm23-H1 and
nm23-H2. For this purpose, 26 human renal carcinoma cell lines and 3
clonal cells subpopulations of the human epitheloid sarcoma cell line GRU-1
were analyzed by means of nm23-H1 and nm23-H2-specific RT-PCR and
followed by the sequencing of the complete open reading frames of nm23-H1
and nm23-H2. In all 26 renal carcinoma cell lines nm23-H1 and nm23-H2 were
detectable at RNA level. In the sequencing of both genes a point mutation
of nm23-H1 was detected in one of the renal carcinoma cell line. However,
by analyzing different passage numbers of this cell line and the primary
tumor, it could be shown that the observed nm23-H1 mutation corresponded
to a cell culture artifact. For nm23-H2, 2 different point mutations could
be detected in a renal carcinoma cell line. However, since these were not
associated with an amino acid exchange, a functional relevance for these
mutations can be excluded. Thus, mutations of nm23-H1 and nm23-H2 in human
renal cell carcinoma appear to be a very rare event unlikely to affect the
genesis and progression of these tumors. In addition, it was demonstrated
for the first time in this work that epitheloid sarcomas also express
nm23-H1 and nm23-H2. However, mutations of both genes could not be detected
in the investigated cell lines, so that the known differences of these cell
lines in biological behavior can not be explained by mutations of nm23-H1
and nm23-H2.
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