Signal transduction pathway activity in adult-type granulosa cell tumor samples

G. J. Brink; J. W. Groeneweg; P. van der Ploeg; G. N. Jonges; E. H. Gort; P. O. Witteveen; R. P. Zweemer; J. M.J. Piek

doi:10.1016/j.ygyno.2025.02.018

Signal transduction pathway activity in adult-type granulosa cell tumor samples

G. J. Brink^*
, J. W. Groeneweg
, P. van der Ploeg
, G. N. Jonges
, E. H. Gort
, P. O. Witteveen
, R. P. Zweemer
, J. M.J. Piek

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Objective: This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC). Methods: STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER). Results: Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity. Conclusions: Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.

Original language	English
Pages (from-to)	6-11
Number of pages	6
Journal	Gynecologic Oncology
Volume	195
DOIs	https://doi.org/10.1016/j.ygyno.2025.02.018
Publication status	Published - Apr 2025

Keywords

Granulosa cell tumor
PI3K pathway
Serous ovarian carcinoma
Signal transduction pathway

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PIIS009082582500054XFinal published version, 813 KBLicence: CC BY

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@article{02350271544641d69640b8233f090006,

title = "Signal transduction pathway activity in adult-type granulosa cell tumor samples",

abstract = "Objective: This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC). Methods: STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER). Results: Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity. Conclusions: Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.",

keywords = "Granulosa cell tumor, PI3K pathway, Serous ovarian carcinoma, Signal transduction pathway",

author = "Brink, \{G. J.\} and Groeneweg, \{J. W.\} and \{van der Ploeg\}, P. and Jonges, \{G. N.\} and Gort, \{E. H.\} and Witteveen, \{P. O.\} and Zweemer, \{R. P.\} and Piek, \{J. M.J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = apr,

doi = "10.1016/j.ygyno.2025.02.018",

language = "English",

volume = "195",

pages = "6--11",

journal = "Gynecologic Oncology",

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TY - JOUR

T1 - Signal transduction pathway activity in adult-type granulosa cell tumor samples

AU - Brink, G. J.

AU - Groeneweg, J. W.

AU - van der Ploeg, P.

AU - Jonges, G. N.

AU - Gort, E. H.

AU - Witteveen, P. O.

AU - Zweemer, R. P.

AU - Piek, J. M.J.

PY - 2025/4

Y1 - 2025/4

N2 - Objective: This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC). Methods: STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER). Results: Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity. Conclusions: Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.

AB - Objective: This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC). Methods: STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER). Results: Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity. Conclusions: Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.

KW - Granulosa cell tumor

KW - PI3K pathway

KW - Serous ovarian carcinoma

KW - Signal transduction pathway

UR - https://www.scopus.com/pages/publications/85219090755

U2 - 10.1016/j.ygyno.2025.02.018

DO - 10.1016/j.ygyno.2025.02.018

M3 - Article

AN - SCOPUS:85219090755

SN - 0090-8258

VL - 195

SP - 6

EP - 11

JO - Gynecologic Oncology

JF - Gynecologic Oncology

ER -

Signal transduction pathway activity in adult-type granulosa cell tumor samples

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