Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UMLS:C0476089 (
endometrial cancer
)
11,379
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are Kunitz-type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI-1 and HAI-2 in
endometrial cancer
. We investigated the biological functions of HAI-1 and HAI-2 using KLE and HEC-251
endometrial cancer
cell lines, thus HAI-1 and HAI-2 were examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. HAI-1 and HAI-2 showed potential inhibitory effects on cell proliferation, migration and cellular invasion by reduction of
matriptase
and hepsin expression. This in turn led to an increase in the levels of E-cadherin and Slug, and a reduction in the levels of Vimentin, SIP1, Snail and Twist, and hence ER and PR signal transduction in
endometrial cancer
cells. The levels of HAI-1 and HAI-2 expression were significantly decreased in
endometrial cancer
specimens relative to the corresponding normal endometrium specimens. Low HAI-1 and HAI-2 expression was a significant predictor for a poor prognosis compared with high HAI-1 and HAI-2 expression. These findings indicate that HAI-1 and HAI-2 could be considered as therapeutic targets and used as favorable prognosis markers for
endometrial cancer
.
...
PMID:The role of hepatocyte growth factor activator inhibitor (HAI)-1 and HAI-2 in endometrial cancer. 2071 9
The effects of specific and non-specific regulation of
matriptase
on
endometrial cancer
cells
in vitro
were investigated. Messenger ribonucleic acid (mRNA) and protein expression of
matriptase
and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B
endometrial cancer
cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on
matriptase
(MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA (
P
< 0.01), and scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of
matriptase
and HAI-1 significantly decreased (
P
< 0.001). Moreover, the invasiveness, metastasis, and survival rate of HEC-1A and RL-952
endometrial cancer
cells were significantly decreased (
P
< 0.001) due to the down-regulation of
matriptase
and HAI-1 upon increasing cisplatin concentration. However, a slight increase in
matriptase
and HAI-1 expression was observed in cells treated with low cisplatin concentration (
P
= 0.01). Moreover,
matriptase
expression was associated with metastasis and invasiveness. Down-regulation of
matriptase
by specific Ma-SiRNA or non-specific cisplatin in
matriptase
/HAI-1-positive
endometrial cancer
cells showed promising therapeutic features.
...
PMID:Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells. 2956 Jan 1
