Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma.

Abstract

OBJECTIVE:

Although treatment for advanced or recurrent endometrial carcinoma has improved over recent years with the introduction of paclitaxel- and platinum-based chemotherapy, in most, the disease remains incurable because of resistance to chemotherapy. In the previous study, we have shown that placental leucine aminopeptidase (P-LAP) is associated with poor prognosis. The objective of this study was to determine whether P-LAP expression affects the chemosensitivity in endometrial carcinoma patients.

METHODS:

Here, we investigated the effect of P-LAP to response for paclitaxel and carboplatin in advanced and recurrence endometrial carcinoma. Furthermore, we transfected P-LAP cDNA into endometrial carcinoma cells (AMEC) and investigated cell growth and apoptosis by paclitaxel or carboplatin.

RESULTS:

In 15 of 17 patients, P-LAP was positive. Twelve of seventeen patients were evaluable for response. Among the eight patients strongly positive for P-LAP, only two patients (25%) showed PR. However, all four patients who were weakly positive for P-LAP showed either complete response (CR) or partial response (PR). P-LAP overexpressor (P-LAP2 and P-LAP8) and a vector control were used to assay chemosensitivity. P-LAP2 clone displayed a 1.7-fold increase in IC(50) against paclitaxel and carboplatin when compared with the vector control, and P-LAP8 clone displayed a 1.6-fold increased in IC(50) against paclitaxel and carboplatin when compared with V1. Compared to vector control cells, apoptotic effect by carboplatin treatment was clearly inhibited in P-LAP2 and P-LAP8 cells. Carboplatin, 10(-6) M, induced the 12.5-fold rate of apoptosis compared to that without treatment at 48 h in vector control cells. However, in P-LAP2 and P-LAP8 clones, 10(-6) M carboplatin induced only 3.2- and 5.1-fold rates of apoptosis, respectively, compared to that of without treatment.

CONCLUSIONS:

P-LAP was suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma.

• Authors: Kiyosumi Shibata, Fumitaka Kikkawa, Chihiro Kondo, Yayoi Mizokami, Hiroaki Kajiyama, Kazuhiko Ino, Seiji Nomura, Shigehiko Mizutani
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 95 Issue 2 Pg. 307-13 (Nov 2004) ISSN: 0090-8258 [Print] United States
• PMID: 15491750 (Publication Type: Journal Article)

Chemical References

• Cystinyl Aminopeptidase
• leucyl-cystinyl aminopeptidase
• Paclitaxel
• Cisplatin

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Apoptosis (drug effects, physiology)
• Carcinoma, Endometrioid (drug therapy, enzymology, genetics, surgery)
• Cell Line, Tumor
• Cisplatin (administration & dosage, pharmacology)
• Cystinyl Aminopeptidase (biosynthesis, genetics, metabolism)
• Drug Screening Assays, Antitumor
• Endometrial Neoplasms (drug therapy, enzymology, genetics, surgery)
• Female
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (drug therapy, enzymology)
• Paclitaxel (administration & dosage, pharmacology)
• Transfection