Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells

Michael G. Borland, Ellen M. Kehres, Christina Lee, Ashley L. Wagner, Brooke E. Shannon, Prajakta P. Albrecht, Bokai Zhu, Frank J. Gonzalez, Jeffrey Maurice Peters

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

To examine the functional role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and PPARγ in skin cancer, stable cell lines were created in the A431 human squamous cell carcinoma cell line. Expression of PPAR target genes was greatly enhanced in response to ligand activation of PPARβ/δ or PPARγ in A431 cells expressing these receptors. PPARβ/δ expression blocked the cell cycle at the G2/M phase, and this effect was increased by ligand activation. Ligand activation of PPARβ/δ markedly inhibited clonogenicity as compared to vehicle-treated controls. Similarly, ligand activation of PPARγ in A431 cells expressing PPARγ resulted in reduced clonogenicity. Expression of either PPARβ/δ or PPARγ markedly reduced tumor volume in ectopic xenografts, while ligand activation of these receptors had little further influence on tumor volume. Collectively, these studies demonstrate that stable expression and activation of PPARβ/δ or PPARγ in A431 cells led to reduced tumorigenicity. Importantly, PPAR expression or ligand activation had major impacts on clonogenicity and/or tumor volume. Thus, PPARβ/δ or PPARγ could be therapeutically targeted for the treatment of squamous cell carcinomas.

Original languageEnglish (US)
Pages (from-to)25-32
Number of pages8
JournalToxicology
Volume404-405
DOIs
StatePublished - Jul 1 2018

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Peroxisome Proliferator-Activated Receptors
Skin
Cell Cycle
Carcinogenesis
Cells
Carcinoma
Chemical activation
Ligands
Tumor Burden
Tumors
Squamous Cell Carcinoma
Cell Line
G2 Phase
Skin Neoplasms

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Borland, Michael G. ; Kehres, Ellen M. ; Lee, Christina ; Wagner, Ashley L. ; Shannon, Brooke E. ; Albrecht, Prajakta P. ; Zhu, Bokai ; Gonzalez, Frank J. ; Peters, Jeffrey Maurice. / Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells. In: Toxicology. 2018 ; Vol. 404-405. pp. 25-32.
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title = "Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells",
abstract = "To examine the functional role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and PPARγ in skin cancer, stable cell lines were created in the A431 human squamous cell carcinoma cell line. Expression of PPAR target genes was greatly enhanced in response to ligand activation of PPARβ/δ or PPARγ in A431 cells expressing these receptors. PPARβ/δ expression blocked the cell cycle at the G2/M phase, and this effect was increased by ligand activation. Ligand activation of PPARβ/δ markedly inhibited clonogenicity as compared to vehicle-treated controls. Similarly, ligand activation of PPARγ in A431 cells expressing PPARγ resulted in reduced clonogenicity. Expression of either PPARβ/δ or PPARγ markedly reduced tumor volume in ectopic xenografts, while ligand activation of these receptors had little further influence on tumor volume. Collectively, these studies demonstrate that stable expression and activation of PPARβ/δ or PPARγ in A431 cells led to reduced tumorigenicity. Importantly, PPAR expression or ligand activation had major impacts on clonogenicity and/or tumor volume. Thus, PPARβ/δ or PPARγ could be therapeutically targeted for the treatment of squamous cell carcinomas.",
author = "Borland, {Michael G.} and Kehres, {Ellen M.} and Christina Lee and Wagner, {Ashley L.} and Shannon, {Brooke E.} and Albrecht, {Prajakta P.} and Bokai Zhu and Gonzalez, {Frank J.} and Peters, {Jeffrey Maurice}",
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Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells. / Borland, Michael G.; Kehres, Ellen M.; Lee, Christina; Wagner, Ashley L.; Shannon, Brooke E.; Albrecht, Prajakta P.; Zhu, Bokai; Gonzalez, Frank J.; Peters, Jeffrey Maurice.

In: Toxicology, Vol. 404-405, 01.07.2018, p. 25-32.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells

AU - Borland, Michael G.

AU - Kehres, Ellen M.

AU - Lee, Christina

AU - Wagner, Ashley L.

AU - Shannon, Brooke E.

AU - Albrecht, Prajakta P.

AU - Zhu, Bokai

AU - Gonzalez, Frank J.

AU - Peters, Jeffrey Maurice

PY - 2018/7/1

Y1 - 2018/7/1

N2 - To examine the functional role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and PPARγ in skin cancer, stable cell lines were created in the A431 human squamous cell carcinoma cell line. Expression of PPAR target genes was greatly enhanced in response to ligand activation of PPARβ/δ or PPARγ in A431 cells expressing these receptors. PPARβ/δ expression blocked the cell cycle at the G2/M phase, and this effect was increased by ligand activation. Ligand activation of PPARβ/δ markedly inhibited clonogenicity as compared to vehicle-treated controls. Similarly, ligand activation of PPARγ in A431 cells expressing PPARγ resulted in reduced clonogenicity. Expression of either PPARβ/δ or PPARγ markedly reduced tumor volume in ectopic xenografts, while ligand activation of these receptors had little further influence on tumor volume. Collectively, these studies demonstrate that stable expression and activation of PPARβ/δ or PPARγ in A431 cells led to reduced tumorigenicity. Importantly, PPAR expression or ligand activation had major impacts on clonogenicity and/or tumor volume. Thus, PPARβ/δ or PPARγ could be therapeutically targeted for the treatment of squamous cell carcinomas.

AB - To examine the functional role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and PPARγ in skin cancer, stable cell lines were created in the A431 human squamous cell carcinoma cell line. Expression of PPAR target genes was greatly enhanced in response to ligand activation of PPARβ/δ or PPARγ in A431 cells expressing these receptors. PPARβ/δ expression blocked the cell cycle at the G2/M phase, and this effect was increased by ligand activation. Ligand activation of PPARβ/δ markedly inhibited clonogenicity as compared to vehicle-treated controls. Similarly, ligand activation of PPARγ in A431 cells expressing PPARγ resulted in reduced clonogenicity. Expression of either PPARβ/δ or PPARγ markedly reduced tumor volume in ectopic xenografts, while ligand activation of these receptors had little further influence on tumor volume. Collectively, these studies demonstrate that stable expression and activation of PPARβ/δ or PPARγ in A431 cells led to reduced tumorigenicity. Importantly, PPAR expression or ligand activation had major impacts on clonogenicity and/or tumor volume. Thus, PPARβ/δ or PPARγ could be therapeutically targeted for the treatment of squamous cell carcinomas.

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