Protocadherin-PC promotes androgen-independent prostate cancer cell growth.
BACKGROUND
Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues.


METHODS
LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization.


RESULTS
PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells. Expression of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells expressed significantly higher levels of PCDH-PC-related mRNA.


CONCLUSIONS
Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells.
Terry
Stephane
S
Department of Urology and Pathology of CHU Henri Mondor, INSERM E 03-37, Université Paris XII, Centre de Recherches Chirurgicales, Assistance Publique des Hôpitaux de Paris, Créteil, France.
Queires
Luis
L
Gil-Diez-de-Medina
Sixtina
S
Chen
Min-Wei
MW
de la Taille
Alexandre
A
Allory
Yves
Y
Tran
Phuong-Lan
PL
Abbou
Claude C
CC
Buttyan
Ralph
R
Vacherot
Francis
F
D000728:Androgens / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000091363:Protocadherins; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051820:TCF Transcription Factors / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D015820:Cadherins; C468654:PCDH11Y protein, human; D000091363:Protocadherins; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051153:Wnt Proteins