Molecular characterization of an improved vector for evaluation of the tumor suppressor versus oncogene abilities of the androgen receptor.
BACKGROUND
There is a growing body of evidence demonstrating that the function of the ligand-occupied androgen receptor (AR) within the nuclei of normal prostatic epithelial cells acts as a tumor suppressor gene. This is in contrast to the well-documented ability of the AR within prostate cancer cells to function as an oncogene. Thus, many groups are attempting to understand the biochemistry and signaling cascade differences involved in the switching of AR from a tumor suppressor to an oncogene.


METHODS
To do this, of plasmid vectors for transgenic expression of AR are very useful. AR negative PC-3 human prostate cancer cells were transfected with a plasmid containing the full length coding sequence of AR without its 5'- or 3'-untranslated regions (UTRs) (i.e., pSG5-AR).


RESULTS
Transgenic expression of the AR protein results in profound growth inhibition which is not relieved by the addition of ligand. A new expression vector for the AR, pAR-IRES-EGFP, has been constructed that contains full-length 5'-UTR which includes the identified translation regulatory regions, the full length coding sequence and the partial 3'-UTR, which includes the identified post-transcriptional regulatory regions. When PC-3 cells were transfected with the pAR-IRES-EGFP vector, it was found that transgenic AR protein expression was not growth inhibitory until ligand was added.


CONCLUSIONS
These pSG5-AR versus pSAR-IRES-EGFP clones are being studied to determine the molecular pathways explaining their different response to AR and ligand.
Litvinov
Ivan V
IV
The Sidney Kimmel Comprehensive Cancer Center, the Graduate Training Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Antony
Lizamma
L
Isaacs
John T
JT
D020121:5' Untranslated Regions / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008297:Male; D009857:Oncogenes / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D011944:Receptors, Androgen