Possible Role of Placental Leucine Aminopeptidase in the Antiproliferative Effect of Oxytocin in Human Endometrial Adenocarcinoma
Purpose: Oxytocin (OT) was reported to inhibit the proliferation of various neoplastic tissues and cells, however, the regulation system remains unclear. This study examined the role of OT and its regulatory ability in endometrial adenocarcinoma. Experimental Design: To investigate the possible func...
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Published in | Clinical cancer research Vol. 9; no. 4; pp. 1528 - 1534 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.04.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: Oxytocin (OT) was reported to inhibit the proliferation of various neoplastic tissues and cells, however, the regulation
system remains unclear. This study examined the role of OT and its regulatory ability in endometrial adenocarcinoma.
Experimental Design: To investigate the possible function of placental leucine aminopeptidase (P-LAP) in endometrial adenocarcinoma, we transfected
P-LAP cDNA into A-MEC cells, showing the lowest enzyme activity of P-LAP. Also we examined P-LAP protein expression in human
endometrial adenocarcinoma.
Results: We demonstrated the presence of P-LAP, which is identical to cystine aminopeptidase as oxytocinase, in human endometrial
adenocarcinoma tissues and found that the expression of P-LAP increase with advances in the grade. Exposure of endometrial
adenocarcinoma cell lines to OT caused dose- and time-dependent inhibition of growth. Treatment with 10 −7 m OT for 72 h reduced cell growth by 62, 25, and 30% in A-MEC, HEC1A, and Ishikawa cells, respectively. P-LAP-transfectant
cells not only partially recovered from OT-induced growth inhibition but also showed a higher growth rate than parental cells
under condition without OT. An OT receptor antagonist and a protein kinase A inhibitor blocked OT-induced growth inhibition
in A-MEC and A-MEC-pc cells but not in A-MEC-LAP cells.
Conclusions: These findings suggested that P-LAP might be functionally positive on carcinoma cell growth by degrading suppressive peptides
such as OT. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |