Analysis of transcriptional activation of a cyclic AMP response element by 2,6,10,14-tetramethylpentadecane (pristane) in JB6 mouse epidermal cells.
Pristane is a naturally occurring isoprenoid that is believed to be derived from the phytyl moiety of chlorophyll. Thus, it is not surprising that pristane is present in many common fruits and vegetables. Furthermore, pristane can be detected in the tissues of fish and mammals. In animal models using rodents, pristane can function as a potent tumor promoter. At the molecular level, pristane can induce changes in the plasma membrane, alter the conformation of chromatin, and selectively activate gene expression. Addition of pristane to a mouse epidermal cell line (JB6 P+) allows these cells to grow in an anchorage-independent manner. In contrast, JB6 P-cells are not transformed by pristane. Our study was undertaken to correlate transformation of P+ cells with changes induced by pristane. Transcriptional activation of a cyclic AMP response element (CRE) was induced by pristane in P+ and P-cells. Point mutations in the CRE abolished activation by pristane, thus indicating that an intact CRE was necessary for pristane activation. In P+ cells, pristane repressed phosphodiesterase activity. However, protein kinase A was activated by pristane in P+ and P-cells. Taken together, these results indicated pristane induced novel changes in P+ cells that in turn may facilitate neoplastic transformation.
Banbura
M
M
Department of Veterinary and Biomedical Science, University of Nebraska at Lincoln 68583-0905.
Ackland-Berglund
C
C
Lee
S H
SH
Hamernik
D
D
Jones
C
C
D051698:Activating Transcription Factor 2; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013729:Terpenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology*; D014466:Ultraviolet Rays
D051698:Activating Transcription Factor 2; D002273:Carcinogens; D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D010726:Phosphodiesterase Inhibitors; D013729:Terpenes; D014157:Transcription Factors; C009042:pristane; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C