PTEN status on gonadotropin-releasing hormone (GnRH) metabolite, GnRH-(1-5), effects in endometrial cancer cell lines migration, & transcriptomic analysis of basal cell line and tumor gene expressions†.

Madelaine Cho-Clark, Gauthaman Sukumar, Sorana Raiciulescu, Clifton Dalgard, Leonardo Mariño-Ramírez, T John Wu

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Article in Biology of reproduction, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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5 · Who and what money

Authors and funding

6 authors.

Madelaine Cho-ClarkDepartment of Gynecologic Surgery & Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Gauthaman SukumarCollaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Sorana RaiciulescuPreventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID 0000-0002-1227-0134

Clifton DalgardCollaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Leonardo Mariño-RamírezNational Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.

T John WuDepartment of Gynecologic Surgery & Obstetrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID 0000-0002-1505-7662

Funding

The GnRH Metabolite, GnRH-(1-5), Functions via an orphan receptor, GPR173R03HD078645 · NICHD · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI WU, T JOHN · 2014 to 2015

$154k

Collaborative Health Initiative Research ProgramDivision of Intramural Research of the National Institute on Minority Health and Health Disparities at the National Institutes of Health 1ZIAMD000016Division of Intramural Research of the National Institute on Minority Health and Health Disparities at the National Institutes of Health 1ZIAMD000018National Institutes of Health Distinguished Scholars ProgramNICHD NIH HHS R03 HD078645NIHUSU RO852488

6 · The paper itself

Abstract

Previous studies have shown that the metabolite of gonadotropin-releasing hormone (GnRH), GnRH-(1-5), promotes migration and invasion in endometrial cancer cell lines through a non-canonical mechanism from its parental peptide. These studies showed that GnRH-(1-5) transactivates the epidermal growth factor receptor/extracellular signal-regulated kinases (EGFR/ERK) signaling pathway through an orphan G-protein-coupled receptor, GPR101, to stimulate matrix metalloproteinase-9 (MMP-9)-mediated EGF release to augment cellular migration and invasion. However, inhibition of the EGFR/ERK signaling pathway showed an incomplete ablation of the effects of GnRH-(1-5) in these studies to suggest that alternative signaling pathways are also involved. Given the incomplete inhibition of GnRH-(1-5) effects by EGFR/ERK pathway blockade, the present study sought to investigate the potential role of transforming growth factor beta (TGF-beta) in complementing the previously observed EGF effects on cellular function. As our previous studies were conducted in Phosphatase and Tensin homolog (PTEN)-negative cell lines, we sought to elucidate the involvement of the TGF-beta signaling pathway and the role of PTEN status in mediating the cellular responses to GnRH-(1-5). The present results show that cellular migration responses to GnRH-(1-5) involve both TGF-beta and EGF signaling pathways and are differentially regulated based on PTEN status. In addition to these cell line studies, we performed differential gene expression analysis of PTEN-positive and PTEN-negative cell lines and tumors using The Cancer Genome Atlas database. Identifying markers associated with PTEN status will allow for a more precise and rapid investigation of GnRH-(1-5) signaling mechanisms in endometrial cancer pathophysiology.

Indexed as

Endometrial NeoplasmsGonadotropin-Releasing HormonePeptide FragmentsPTEN PhosphohydrolaseCell Line, TumorCell MovementEpidermal Growth FactorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMutationSignal TransductionTransforming Growth Factor betaEpidermal Growth FactorGonadotropin-Releasing HormoneLHRH (1-5)Peptide FragmentsPTEN PhosphohydrolasePTEN protein, humanTransforming Growth Factor betabiomarkersendometrial cancergonadotropin-releasing hormone (GnRH)phosphatase and tensin homolog (PTEN)signaling pathwaystransforming growth factor-beta (TGF-beta)

Identifiers

PMID40709821

DOI10.1093/biolre/ioaf168

PMCPMC12706474

What Socratic holds

Textmetadata

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.