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.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Shibata K,Kikkawa F,Kondo C,Mizokami Y,Kajiyama H,Ino K,Nomura S,Mizutani S

doi

10.1016/j.ygyno.2004.07.054

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

307-13

issue

2

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(04)00567-0

journal_volume

95

pub_type

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