[Regulation of insulin-like growth factors and NF-kappaB by proteasome system in endometrial cancer].
Insulin-like growth factors and the nuclear factor kappaB (NF-kappaB) are known to play an important role in pathogenesis of endometrial cancer. However, there is still uncertainty about their proteolytic regulation. We studied the correlation between chymotrypsin-like activity ofproteasomes and IGF-I, IGF-II and NF-kappaB levels in endometrial cancer tissues. The total activity of proteasomes and the 20S and 26S proteasome activities were shown to be significantly higher in malignant tumors than in unaltered endometrium. Negative correlations between the 26S proteasome activity and NF-kappaBp50 level as well as between the 26S and 20S proteasome activities and IGF-I level were found. The data obtained indicate a possible proteasome regulation of growth and transcription factors. As it is considered that the major pool of IGF-I is located in the extracellular space, it is likely that extracellular proteasomes also take part in the regulation of IGF-I content. The positive correlation between IGF-I level and PAPP-A metalloproteinase gives evidence that this proteolytic enzyme is another important regulator of growth factor level, which provides proteolysis of IGF-I binding proteins and increasing IGF-I concentration in tissues. The present data show possibility of proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.
L V
LV
Spirina
N V
NV
Bochkareva
I V
IV
Kondakova
L A
LA
Kolomiets
E E
EE
Shashova
V D
VD
Koval'
A L
AL
Chernysheva
O N
ON
Asadchikova
D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction / Q000235:genetics
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011266:Pregnancy-Associated Plasma Protein-A; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease