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Data from: Ovarian BDNF promotes survival, migration, and attachment of tumor precursors originated from p53 mutant fallopian tube epithelial cells

Citation

Yang-Hartwich, Yang et al. (2020), Data from: Ovarian BDNF promotes survival, migration, and attachment of tumor precursors originated from p53 mutant fallopian tube epithelial cells, Dryad, Dataset, https://doi.org/10.5061/dryad.dv41ns1vd

Abstract

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological malignancy. New evidence supports a hypothesis that HGSOC can originate from fallopian tube epithelium (FTE). It is unclear how genetic alterations and pathophysiological processes drive the progression of FTE tumor precursors into widespread HGSOCs. In this study, we uncovered that brain-derived neurotrophic factor (BDNF) in the follicular fluid stimulates the tropomyosin receptor kinase B (TrkB)-expressing FTE cells to promote their survival, migration, and attachment. Using in vitro and in vivo models, we further identified that the acquisition of common TP53 gain-of-function (GOF) mutations in FTE cells led to enhanced BDNF/TrkB signaling comparing to that of FTE cells with TP53 loss-of-function (LOF) mutations. Different mutant p53 proteins can either increase TrkB transcription or enhance TrkB endocytic recycling. Our findings have demonstrated possible interplays between genetic alterations in FTE tumor precursors (i.e., p53 gain-of-function mutations) and pathophysiological processes (i.e., the release of follicular fluid upon ovulation) during the initiation of HGSOC from the fallopian tube. Our data revealed molecular events underlying the link between HGSOC tumorigenesis and ovulation, a physiological process that has been associated with risk factors of HGSOC.

Methods

FTE240 cells were treated with BDNF 50ng/ml in 3D culture for 24 hours. Untreated cells were cultured under the same condition as control. Three biological repeats were included in the experiment, in which three different batches of FTE240 cells were utilized. Each repeat included untreated control and BDNF-treated groups. RNA was extracted and analysed using Clariom D Human Transcriptome Array and GeneChip Scanner 3000 7G system (Thermo Fisher Scientific, Waltham, MA). Transcriptome Analysis Console software was used to analyse the array data. The RNA expression was compared between the paired samples of untreated control and BDNF-treated groups.

Funding

Office of the Assistant Secretary of Defense for Health Affairs, Award: W81XWH-15-1-0221

National Institutes of Health, Award: R03 CA216127

Discovery To Cure

Office of the Assistant Secretary of Defense for Health Affairs, Award: W81XWH-15-1-0221