Second messenger up-regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines, PC-3 and DU-145.
A theoretical pathway of transcriptional regulation of the androgen receptor (AR) gene is via a cAMP response element (CRE) present in its promoter region (-508 to -501). After 20 h of stimulation with 8-bromo-cAMP, AR mRNA was upregulated in LNCaP but not in either PC-3 or DU-145 cell lines. We have demonstrated that the level of CRE binding protein (CREB) was the same in all cell lines and that the putative AR-CRE forms specific and compatible protein interactions with CREB. The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC-3 and DU-145 cell lines. This may be an important primary mechanism of androgen insensitivity in prostate cancer.
Stubbs
A P
AP
Department of Histopathology, Royal Postgraduate Medical School Hammersmith Hospital, London, UK.
Lalani
E N
EN
Stamp
G W
GW
Hurst
H
H
Abel
P
P
Waxman
J
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000378:metabolism; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011817:Rabbits; D011944:Receptors, Androgen / Q000096:biosynthesis*; D012156:Reticulocytes / Q000378:metabolism; D015290:Second Messenger Systems; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D012333:RNA, Messenger; D011944:Receptors, Androgen