The antiproliferative effects of PPARgamma ligands in normal human mammary epithelial cells.
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor in the steroid nuclear receptor superfamily. Ligand activation of PPARgamma is associated with differentiation and an inhibition of proliferation in normal and malignant cells, including adipocytes, monocytes, and tumor cells in colon, prostate, and breast cancers. The current studies were undertaken to assess both the expression and functional activity of PPARgamma in cultured normal human mammary epithelial cells (HMECs) and tissue samples. Analyses by northern hybridization, immunoblotting, and immunohistochemistry demonstrate PPARgamma gene expression in HMECs and breast tissue specimens. DNA binding and transactivation assays indicate the presence of functionally active PPARgamma in HMECs. Treatment with PPARgamma selective ligands, 15-deoxy-delta-(12,14)-prostaglandin J2 (15dPGJ2) and ciglitazone, inhibits the growth of HMECs in a dose-dependent manner. This growth inhibition is associated with alterations in cell cycle progression and the induction of apoptosis.
Yee
Lisa D
LD
Department of Surgery, The Ohio State University, Columbus, OH 43210, USA. yee.52@osu.edu
Guo
Yan
Y
Bradbury
Jamie
J
Suster
Saul
S
Clinton
Steven K
SK
Seewaldt
Victoria L
VL
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001940:Breast / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008024:Ligands; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
C477819:15-deoxyprostaglandin J2; D007004:Hypoglycemic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D015230:Prostaglandin D2; C039671:ciglitazone