The hormone replacement therapy drug tibolone acts very similar to medroxyprogesterone acetate in an estrogen-and progesterone-responsive endometrial cancer cell line.
Tibolone, a steroidogenic compound with both estrogenic and progestagenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. We have evaluated whether the effect of tibolone on a human endometrial cell line is similar to, or comparable with, the effect of estradiol (E(2)), medroxyprogesterone acetate (MPA) or E(2) + MPA treatment. Using stable transfection techniques, the estrogen receptor (ER) expressing human endometrial cancer cell line, ECC1, was altered to also express both progesterone receptors (PRs). These cells were then used to assess growth regulation and expression profiling (Affymetrix U133plus2) under the influence of E(2) (1 nM), MPA (1 nM), E(2) + MPA or tibolone (100 nM). Growth assessment and comparison of profiles indicate that tibolone behaves predominantly like MPA. Furthermore, regulation of prereplication complex genes, such as the minichromosome maintenance genes, could be involved in the observed strong inhibition of growth by tibolone as well as MPA. In addition, in total, 15 genes were found to be specific for tibolone treatment. These genes were predominantly involved in regulation of the cell cycle and differentiation.
Hanifi-Moghaddam
P
P
Department of Reproduction and Development, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands. p.hanifi_moghaddam@erasmusmc.nl
Sijmons
B
B
Ott
M C
MC
van Ijcken
W F J
WF
Nowzari
D
D
Kuhne
E C M
EC
van der Spek
P
P
Kloosterboer
H J
HJ
Burger
C W
CW
Blok
L J
LJ
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020249:Hormone Replacement Therapy; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009652:Norpregnenes / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D004967:Estrogens; D009652:Norpregnenes; D011374:Progesterone; D017258:Medroxyprogesterone Acetate; C027385:tibolone