Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin G1 protein is expressed in normal endometrial epithelial cells in a progesterone-dependent manner. It is an important mediator of the inhibiting effect of progesterone on cell proliferation. Moreover, the expression of cyclin G1 is also found to be decreased in human endometrial carcinoma cells (ECCs). To study the mechanism of decrease in the expression levels of cyclin G1, 3 ECC cell lines, Ishikawa, HEC-1-B, and KLE cells were treated with progesterone (P(4)). The KLE cells, in which progesterone receptor (PR) expression was absent, were transfected with PR-expressing plasmid before treatment with P(4). The results showed that cyclin G1 expression increased in Ishikawa and HEC-1-B cells after treatment with P(4), additionally the cell proliferation was suppressed but not in KLE cells. When the PR-expressing plasmid was transfected into KLE cells, the effect of P(4) was restored. Our data suggest that the deficiency of progesterone and its receptors is an important cause of the decreased expression of cyclin G1 in endometrial carcinoma, which may account for carcinogenesis and development of endometrial carcinomas.
 ...
PMID:The role of progesterone and its receptor on cyclin G1 expression in endometrial carcinoma cells. 2264 21

Cyclin G1 is the only cyclin that has either positive or negative effects on cell growth. Our previous study found decreased expression of cyclin G1 in human endometrial carcinoma tissues compared with normal endometrial tissues. The study aimed to evaluate cyclin G1 expression and its effect on proliferation of human endometrial carcinoma cells (ECCs). Cyclin G1-GFP (green fluorescence protein) plasmid was constructed and transfected into various differentiated human ECCs, including Ishikawa, HEC-1-B and KLE cells, and proliferation of the transfected cells was determined by the CCK-8 method. Exogenous cyclin G1 mRNA and protein were measured by RT-PCR and Western blot, respectively, and GFP signal was monitored by fluorescence microscopy. Chinese hamster ovary (CHO) cells were transfected with the same constructs as a cell control. Cyclin G1-GFP-transfected Ishikawa cells were further treated with MG132, an inhibitor of proteasome, to analyze if low expression of cyclin G1 is related to its abnormal degradation in ECCs. Ectopic expression of exogenous cyclin G1 was found to significantly suppress the proliferation of Ishikawa and HEC-1-B cells but not KLE cells. Compared with cyclin G1-transfected CHO cells, exogenous cyclin G1 protein expression was low in Ishikawa and HEC-1-B cells, and was undetectable in KLE cells. However, all ECC lines and CHO cells expressed similar levels of exogenous cyclin G1 and GFP mRNA. MG132 treatment increased cyclin G1 protein expression in cyclin G1-GFP-transfected Ishikawa cells. This is the first study to present evidence to suggest that cyclin G1 exerts negative control on proliferation of ECCs. Exogenous cyclin G1 shows different protein expression levels in ECCs with different malignancies, and cyclin G1 protein is highly unstable and is rapidly degraded in ECCs.
 ...
PMID:Effects of expression of exogenous cyclin G1 on proliferation of human endometrial carcinoma cells. 2358 24

Under normal conditions, progesterone inhi-bits the estrogen-induced proliferation of endometrial epithelium. Our previous studies have shown that cyclin G1 was progesterone-dependent in mouse endometrial epithelium at peri-implantation, and exogenous cyclin G1 suppressed the proliferation of endometrial cancer cells. The objectives of this study are to determine whether cyclin G1, as a negative regulator of the cell cycle, is involved in the antiproliferative action of progesterone on endometrial epithelial cells, and to explore the possible molecular mechanism of cyclin G1 inhibition. The siRNA-mediated elimination of cyclin G1 attenuated the antiproliferative action of progesterone on endometrial epithelial cells. Immunoprecipitation showed that progesterone-induced cyclin G1 could interact with PP2A to mediate its phosphatase activity. The block of PP2A activity also attenuated the antiproliferative action of progesterone on endometrial epithelial cells and increased the phosphorylated Rb. In conclusion, progesterone-induced cyclin G1 mediates the inhibitory effect of progesterone on endometrial epithelial cell proliferation possibly through the recruitment of PP2A to dephosphorylate Rb.
...
PMID:Progesterone-induced cyclin G1 inhibits the proliferation of endometrial epithelial cell and its possible molecular mechanism. 2500 70