Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement.
TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.
Bidaux
G
G
Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Bâtiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
Roudbaraki
M
M
Merle
C
C
Crépin
A
A
Delcourt
P
P
Slomianny
C
C
Thebault
S
S
Bonnal
J-L
JL
Benahmed
M
M
Cabon
F
F
Mauroy
B
B
Prevarskaya
N
N
D043582:5-alpha-Dihydroprogesterone / Q000378:metabolism / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D020218:Response Elements; D050053:TRPM Cation Channels; D014407:Tumor Cells, Cultured
D000728:Androgens; D007473:Ion Channels; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D043582:5-alpha-Dihydroprogesterone