title: Involvement of PTEN in TPA-mediated p53-activation in mouse skin epidermal JB6 cells.
abstract: Our recent studies suggest a unique role of p53 during the early stage of cancer development. However, how p53 activation is regulated during TPA treatment remains elusive. We used murine skin epidermal JB6 promotion-sensitive (P+) and promotion resistant (P-) cells to observe differential expression of PTEN during TPA-induced p53 activation. Total PTEN expression was decreased in only P+ cells. Nuclear expression of PTEN increased and complex formation between PTEN and p53 occurred in P+ cells treated with TPA. Knocking down PTEN expression via siRNA inhibited TPA-induced Bax expression. Similar effects were seen with the p53 inhibitor, pifithrin-alpha. Cells that were transfected with siRNA to PTEN exhibited enhanced tumorigenicity. Our findings suggest PTEN mediates TPA-induced p53 activation.
authors.affiliation: Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA.
authors.forename: Delira
authors.initials: D
authors.lastname: Robbins
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Ponville
authors.forename: Kerri
authors.initials: K
authors.lastname: Morris
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D034741:RNA, Small Interfering; D012867:Skin; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C431843:tris(2-pyridylmethyl)amine; D014050:Toluene; C121565:pifithrin; D051059:PTEN Phosphohydrolase