Steroid-modulated proliferation of human endometrial carcinoma cell lines: any role for insulin-like growth factor signaling?
OBJECTIVE
Estrogen-stimulated proliferation of the normal and malignant human endometrium is balanced by the differentiating properties of progesterone. This study evaluated the role of insulin-like growth factor (IGF) signaling in steroid-induced modulation of endometrial cancer cell proliferation.


METHODS
We used the human endometrial, estrogen-responsive ECC-1 and progesterone-responsive PRAB-36 cell lines. Proliferation studies with IGFs in combination with either estrogen or progesterone were conducted. Furthermore, the mRNA and protein expression of insulin-like growth factor-binding proteins (IGFBPs) was evaluated.


RESULTS
Using the ECC-1 cell line, we observed that estrogen-induced proliferation is modulated via the IGF-receptor signaling pathway, and that IGF-1-induced stimulation of proliferation does not influence estrogen receptor signaling. Furthermore, expression of the main modulators of IGF action, the IGFBPs, was found to be regulated by estrogen and progesterone in both cell lines. IGFBP-4 was up-regulated by estrogen in the ECC-1 cell line, and IGFBP-3 and IGFBP-6 were down-regulated by progesterone in the PRAB-36 cell line.


CONCLUSIONS
Estrogen-induced stimulation of proliferation of ECC-1 endometrial cancer cells is partly achieved via IGF signaling. Furthermore, the IGFBPs are regulated by estrogens as well as progestagens and could potentially play a role in the modulation of endometrial cancer cell proliferation.
Gielen
Susanne C J P
SC
Department of Obstetrics, Erasmus Medical Center, Rotterdam, The Netherlands. s.gielen@erasmusmc.nl
Hanekamp
Eline E
EE
Blok
Leen J
LJ
Huikeshoven
Frans J
FJ
Burger
Curt W
CW
D002277:Carcinoma / Q000473:pathology*; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000473:pathology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis; D015398:Signal Transduction; D013002:Somatomedins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D004967:Estrogens; D018974:Insulin-Like Growth Factor Binding Protein 4; D013002:Somatomedins