Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative
tumour suppressor
gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3,
RPS6KA2
) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that
RPS6KA2
is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of
RPS6KA2
with an alternative start codon. Homozygous deletions were identified within the
RPS6KA2
gene in two cell lines. Re-expression of
RPS6KA2
in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of
RPS6KA2
reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against
RPS6KA2
showed the opposite effect in 41M cells. The above results suggest that
RPS6KA2
is a putative
tumour suppressor
gene to explain allele loss at 6q27.
...
PMID:RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer. 1687 54
