Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells - PubMed (original) (raw)
. 2002 Apr 17;94(8):617-29.
doi: 10.1093/jnci/94.8.617.
Affiliations
- PMID: 11959895
- DOI: 10.1093/jnci/94.8.617
Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells
Viqar Syed et al. J Natl Cancer Inst. 2002.
Abstract
Background: Reproductive hormones are associated with risk for epithelial ovarian cancer. To determine the effect of such hormones on the activation of interleukin 6 (IL-6)/STAT3 (signal transducer and activator of transcription-3) signaling, which may be involved in ovarian cancer, we investigated the status of STAT3, IL-6, and its receptor in immortalized human ovarian surface epithelial (HOSE) and ovarian cancer (OVCA) cell lines.
Methods: Two immortalized HOSE cell lines and two OVCA cell lines were cultured with gonadotropins, sex steroid hormones, and/or IL-6, alone or with specific inhibitors or IL-6-neutralizing antibodies. Expression of IL-6, the IL-6 receptor alpha chain (IL-6Ralpha), and phosphorylated and unphosphorylated STAT3 messenger RNAs (mRNAs) and proteins in all cells was determined. Cell proliferation and soft-agar colony formation were assessed. STAT3 activity was investigated in OVCA cells transfected with a dominant negative STAT3 (Dn-STAT3), wild-type STAT3, or an empty control vector. All statistical tests were two-sided.
Results: Levels of IL-6 mRNA and protein increased in all cells treated with follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17beta-estradiol, or estrone but increased only in OVCA cells treated with testosterone and 5alpha-dihydrotestosterone. For all lines, IL-6 antibodies partially inhibited hormone-stimulated cell proliferation but completely inhibited IL-6-enhanced cell proliferation. IL-6 induced STAT3 phosphorylation and activation in HOSE cells; STAT3 was constitutively activated in OVCA cells. Higher levels of IL-6Ralpha and STAT3 transcription factors were observed in OVCA cells than in HOSE cells. After transfection, Dn-STAT3 suppressed endogenous STAT3 and inhibited all forms of IL-6-stimulated OVCA cell proliferation (OVCA 429 cells, P<.001; OVCA 432 cells, P<.006), whereas wild-type STAT3 enhanced HOSE cell proliferation (wild-type STAT3 at 0.5 microg/mL in HOSE 306 cells, P<.002; STAT3 at 1.0 microg/mL in HOSE 306 or both concentrations of wild-type STAT3 in HOSE 642 cells, P<.001).
Conclusions: The IL-6/STAT3 signaling pathway may mediate FSH-, LH-, and estrogen-stimulated HOSE cell proliferation. Increased IL-6Ralpha expression and constitutive STAT3 activation may be associated with ovarian cancer.
Comment in
- Re: Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells.
Auersperg N, Ziltener H. Auersperg N, et al. J Natl Cancer Inst. 2002 Aug 21;94(16):1255-6. doi: 10.1093/jnci/94.16.1255. J Natl Cancer Inst. 2002. PMID: 12189232 No abstract available.
Similar articles
- Profiling follicle stimulating hormone-induced gene expression changes in normal and malignant human ovarian surface epithelial cells.
Ho SM, Lau KM, Mok SC, Syed V. Ho SM, et al. Oncogene. 2003 Jul 3;22(27):4243-56. doi: 10.1038/sj.onc.1206437. Oncogene. 2003. PMID: 12833147 - Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.
Hirano T, Ishihara K, Hibi M. Hirano T, et al. Oncogene. 2000 May 15;19(21):2548-56. doi: 10.1038/sj.onc.1203551. Oncogene. 2000. PMID: 10851053 Review. - Interleukin-6/interleukin-6 receptor pathway as a new therapy target in epithelial ovarian cancer.
Dijkgraaf EM, Welters MJ, Nortier JW, van der Burg SH, Kroep JR. Dijkgraaf EM, et al. Curr Pharm Des. 2012;18(25):3816-27. doi: 10.2174/138161212802002797. Curr Pharm Des. 2012. PMID: 22591418 Review.
Cited by
- Secreted Soluble Factors from Tumor-Activated Mesenchymal Stromal Cells Confer Platinum Chemoresistance to Ovarian Cancer Cells.
Koren Carmi Y, Khamaisi H, Adawi R, Noyman E, Gopas J, Mahajna J. Koren Carmi Y, et al. Int J Mol Sci. 2023 Apr 23;24(9):7730. doi: 10.3390/ijms24097730. Int J Mol Sci. 2023. PMID: 37175439 Free PMC article. - Characterizing Endocrine Status, Tumor Hypoxia and Immunogenicity for Therapy Success in Epithelial Ovarian Cancer.
Pereira M, Matuszewska K, Jamieson C, Petrik J. Pereira M, et al. Front Endocrinol (Lausanne). 2021 Nov 17;12:772349. doi: 10.3389/fendo.2021.772349. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 34867818 Free PMC article. Review. - A Comprehensive Molecular and Clinical Analysis of the piRNA Pathway Genes in Ovarian Cancer.
Lee E, Lokman NA, Oehler MK, Ricciardelli C, Grutzner F. Lee E, et al. Cancers (Basel). 2020 Dec 22;13(1):4. doi: 10.3390/cancers13010004. Cancers (Basel). 2020. PMID: 33374923 Free PMC article. - Prognostic and Clinical Value of Interleukin 6 and CD45+CD14+ Inflammatory Cells with PD-L1+/PD-L2+ Expression in Patients with Different Manifestation of Ovarian Cancer.
Wertel I, Suszczyk D, Pawłowska A, Bilska M, Chudzik A, Skiba W, Paduch R, Kotarski J. Wertel I, et al. J Immunol Res. 2020 Sep 30;2020:1715064. doi: 10.1155/2020/1715064. eCollection 2020. J Immunol Res. 2020. PMID: 33062717 Free PMC article. - Interleukin-6-mediated resistance to immunotherapy is linked to impaired myeloid cell function.
Beyranvand Nejad E, Labrie C, van der Sluis TC, van Duikeren S, Franken KLMC, Roosenhoff R, Arens R, van Hall T, van der Burg SH. Beyranvand Nejad E, et al. Int J Cancer. 2021 Jan 1;148(1):211-225. doi: 10.1002/ijc.33280. Epub 2020 Sep 7. Int J Cancer. 2021. PMID: 32875568 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Miscellaneous