Dataset Information

Co-mutations of CTNNB1 and PTEN Synergistically Promote EMT and Drive Aggressive Tumor Progression in Endometrial Cancer.

ABSTRACT: Endometrioid endometrial cancer (EEC) is the most common gynecologic malignancy, with poor outcomes in advanced stages. Co-mutations in PTEN and CTNNB1 are frequent and linked to poor prognosis, but their functional roles remain unclear. Using uterine-specific Pten knockout and stabilized β-catenin mutant mice (Pgrcre/+Ptenf/fCtnnb1f(ex3)/+; Ptend/dCtnnb1f(ex3)/+), we found markedly reduced survival, early-onset invasive adenocarcinoma, and aggressive metastatic disease compared to Pgrcre/+Ptenf/f; Ptend/d mice. Transcriptomic and histopathological analyses revealed activation of oncogenic pathways (WNT/β-catenin, PI3K/AKT, Hedgehog, EMT), with loss of E-cadherin and upregulation of SNAIL confirming EMT. These findings show that PTEN–CTNNB1 co-mutations synergistically drive EMT and tumor progression, defining a distinct aggressive subtype of EEC.

ORGANISM(S): Mus musculus

PROVIDER: GSE319686 | GEO | 2026/03/21

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other
	GSE319686_PtenEx3_RNA_Matrix.txt.gz	Txt

Items per page:

1 - 2 of 2

Similar Datasets

Project description:Stable activation of the WNT signaling effector beta-catenin (CTNNB1(ex3) in ovarian granulosa cells results in the formation of premalignant lesions that develop into granulosa cell tumors (GCTs) spontaneously later in life. Loss of the tumor suppressor gene Pten accelerates GCT formation in the CTNNB1 strain. Conversely, expression of oncogenic KRASG12D causes the dramatic arrest of proliferation, differentiation and apoptosis in granulosa cells, and consequently, small abnormal follicle-like structures devoid of oocytes accumulate in the ovary. Because of the potent anti-proliferative effects of KRASG12D in granulosa cells, we sought to determine if KRASG12D would block precancerous lesion and tumor formation in follicles of the CTNNB1 mutant mice. Unexpectedly, transgenic Ctnnb1;Kras mutant mice developed early-onset GCTs leading to premature death in a manner similar to theCtnnb1;Pten mutant mice. Moreover, the GCTs in the Ctnnb1;Kras mutant mice exhibited increased GC proliferation, decreased apoptosis and impaired differentiation. Microarray and RT-PCR analyses revealed that ovaries from mice expressing dominant-stable CTNNB1 with either Pten loss or KRAS activation were unpredictably similar. Specifically, gene regulatory processes induced by CTNNB1 were mostly enhanced by either KRAS activation or Pten loss in remarkably similar patterns and degree. Furthermore, the concomitant activation of CTNNB1 and KRAS in Sertoli cells resulted in the development of granulosa cell tumors of the testis. RT-PCR studies showed a partial overlap in gene regulatory processes associated with tumor development in the ovary and testis. Together, these results suggest that KRAS activation and Pten loss induce GCT development from premalignant lesions via highly similar molecular mechanisms. four samples: average of two wild type samples (previously submitted as GSM403220 and GSM403221), beta-Catenin constitutively active mutant, beta-Catenin;Pten double mutant, and beta-Catenin;Kras(G12D) double mutant

Dataset Information

Co-mutations of CTNNB1 and PTEN Synergistically Promote EMT and Drive Aggressive Tumor Progression in Endometrial Cancer.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets