Early effects of high concentrations of progesterone and mifepristone A gene expression study of endometrial cancer cells (Ishikawa).
Patients with endometrial hyperplasia representing preliminary stages of endometrial cancer have shown to respond to therapy in 100% of the cases when treated with levonorgestrel-impregnated intrauterine device. Anti-proliferative effect has also been reported after application of an anti-progestin impregnated intrauterine device which showed to induce endometrial atrophy. The intention of the present study was to obtain more information of novel therapeutic targets for hormonal treatment in endometrial hyperplasia and endometrial cancers. Gene expression of signaling pathways after stimulation of Ishikawa cells with high doses of progesterone (32 microM) or Mifepristone (32 microM) was performed. After using an oligo microarrays representing 24,650 human genes and 37,580 gene transcripts, 6154 genes remained after pre-processing and filtering. This resulted in a total of 993 up-regulated genes with 189 genes for progesterone and 255 genes for Mifepristone. The 550 down-regulated genes were distributed with 256 genes for progesterone, 127 genes for RU 486. The results showed that genes presenting the epidermal growth factor (EGF)/MAP-kinase pathway were significantly over-represented by progesterone treatment, whereas, by Mifepristone treatment genes involved in the p53 pathway were also up-regulated (data not shown). These genes may be interesting as potential new therapeutic targets in endometrial hyperplasia and endometrial cancer, as candidate genes for therapy response or as candidate markers for tumor progression.
Ørbo
Anne
A
Department of Pathology, University Hospital of North-Norway, N-9038 Tromsø, Norway. anne.orbo@fagmed.uit.no
Moe
Bjørn T
BT
Grønaas
Halvor
H
Paulssen
Ruth H
RH
D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D011372:Progestins; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone; D004815:Epidermal Growth Factor