GnRH agonist inhibits human telomerase reverse transcriptase mRNA expression in endometrial cancer cells.
We investigated the relationship between the antiproliferative effect of GnRH agonist and telomerase activity using the endometrial cancer cell line HEC-1A. The subjects were 38 endometrial cancer, and 2 atypical endometrial hyperplasia patients. GnRH-R expression was detected using RT-PCR. HEC-1A cells were incubated with 10(-7)-10(-4) M GnRH agonist (leuprolide acetate), and cell proliferation was determined using MTT assay. The telomerase activity was detected by the TRAP assay and expression of human telomerase reverse transcriptase (hTERT) was assessed by RT-PCR. GnRH-R mRNA was detected at 94.7% (36/38) in endometrial cancer and in both of the atypical endometrial hyperplasia and in HEC-1A cells. Cell proliferation of HEC-1A showed significant inhibition at leuprolide acetate concentrations of 10(-6) M or higher compared with untreated control culture (p<0.05). The telomerase activity showed no marked difference compared with untreated culture. However, hTERT mRNA expression showed a decrease in the leuprolide-treated cells. It is suggested that the mechanism of the antitumor effect of GnRH agonist involved the inhibition of hTERT mRNA expression in the endometrial cancer cells.
Nagai
Nobutaka
N
Department of Obstetrics and Gynecology, Hiroshima University Faculty of Medicine, Hiroshima, Japan. nnagai@hiroshima-u.ac.jp
Oshita
Takafumi
T
Mukai
Keiji
K
Shiroyama
Yuko
Y
Shigemasa
Kazushi
K
Ohama
Koso
K
D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D011966:Receptors, LHRH / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D019098:Telomerase; D016729:Leuprolide