ArticlePloS one2012
Transforming growth factor alpha (TGFα) regulates granulosa cell tumor (GCT) cell proliferation and migration through activation of multiple pathways.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Female Age Affects the Mesenchymal Stem Cell Characteristics of Aspirated Follicular Cells in the In Vitro Fertilization Programme.Stem cell reviews and reports · 2019Trial
- Dysregulated post‑translational modifications in granulosa cells drive ovarian dysfunction and potential infertility applications (Review).International journal of molecular medicine · 2026Review
- Adult Granulosa Cell Tumor With Low-Level Amplifications ofCase reports in urology · 2026Article
- Elevated expression and secretion of TGF-α contribute to Temozolomide resistance in human glioblastoma cells.Cancer cell international · 2025Article
- Regulation of inflammatory lung injury and repair by transforming growth factors.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Dysregulations of Key Regulators of Angiogenesis and Inflammation in Abdominal Aortic Aneurysm.International journal of molecular sciences · 2023Article
- EP300 facilitates human trophoblast stem cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells.Cell death & disease · 2023Article
- Immunohistochemical markers of prognosis in adult granulosa cell tumors of the ovary - a review.Journal of ovarian research · 2023Review
- HB-EGF upregulates StAR expression and stimulates progesterone production through ERK1/2 signaling in human granulosa-lutein cells.Cell communication and signaling : CCS · 2022Article
- Stimulatory effects of TGFα in granulosa cells of bovine small antral follicles.Journal of animal science · 2022Article
- Cisplatin inhibits the proliferation of Saos-2 osteosarcoma cells via the miR-376c/TGFA pathway.Bosnian journal of basic medical sciences · 2021Article
- Four and a Half LIM Domains 2 (FHL2) Contribute to the Epithelial Ovarian Cancer Carcinogenesis.International journal of molecular sciences · 2020Article
- Reprogramming of Ovarian Granulosa Cells by YAP1 Leads to Development of High-Grade Cancer with Mesenchymal Lineage and Serous Features.Science bulletin · 2020Article
- Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro†.Biology of reproduction · 2019Article
- Timely expression and activation of YAP1 in granulosa cells is essential for ovarian follicle development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers.Oncology reports · 2019Article
- RUNX3 Promotes the Tumorigenic Phenotype in KGN, a Human Granulosa Cell Tumor-Derived Cell Line.International journal of molecular sciences · 2019Article
- YAP1-LATS2 feedback loop dictates senescent or malignant cell fate to maintain tissue homeostasis.EMBO reports · 2019Article
- Low plasma stem cell factor combined with high transforming growth factor-α identifies high-risk patients in pulmonary arterial hypertension.ERJ open research · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.
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