Mp68-08 a ‘broken Ctcf’ Gene Signature, a Master Epigenetic Regulator, Predicts Adverse Cancer Outcome and Altered Amino Acid Transport in Prostate Cancer.
Year: 2019
Type: article
Abstract: were compared for WNT10B using IHC Real-Time RT PCR: RNA isolated using RNeasy kit, reverse transcribed with iScript and quantified using BioRad SoSoAdvanced SYBR kit.Stable knockdown: WNT10B and Control lentiviral constructs were used to create stable WNT10B knockdown in PC3 cells Cell Proliferation Assay: MTT assay assessed proliferation Side Population Analysis: Hoechst exclusion assay was used to assess stem-like cell side population Xenograft development: Primary xenografts were developed subcutaneously in nude mice and harvested at 30 days.Serial transplantation was performed subcutaneously and under the renal capsule with harvest at 9 weeks.RESULTS: Wnt10b ontogeny rapidly declines postnatally in rat VP.Exogenous Wnt10b in developing VPs decreased growth suggesting an antiproliferative role.VPs from PB-SV40 LTag rats with localized PCa showed 25 fold reduction in Wnt10b mRNA and in protein levels.WNT10B protein levels in localized human PCa specimens ranging from Gleason grades 6-8 were reduced on IHC compared to benign regions.However, WNT10B levels were increased in metastatic cell line PC3 compared to benign epithelial cells suggesting cancer stage-specific roles.WNT10B knockdown in PC3 cells increased proliferation but reversed expression of EMT genes, reduced stemness and MMP genes, and reduced stem celllike cells.Furthermore, loss of WNT10B abrogated ability of PC3 cells to propagate tumors via serial transplantation.CONCLUSIONS: These results indicate dual and opposing roles for WNT10B in normal development and in PCa progression.Decreased WNT10B levels in localized cancer allow for a hyperproliferative state and increased levels in advanced disease confers stemness and malignant propensity which is mitigated by WNT10B knockdown.This identifies WNT10B as a potential target for therapeutic intervention in PCa.
Source: The Journal of Urology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2941191330