The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells.
We analyzed expression status of the recently identified tumor suppressor geneRASSF1A in primary prostate carcinomas and in prostate cell lines. We found complete methylation of the RASSF1A promoter in 63% of primary microdissected prostate carcinomas (7 of 11 samples). The remaining 4 samples (37%) were partially methylated, possibly because of contamination with normal cells. No promoter methylation was observed in matching normal prostate tissues. High levels of RASSF1A transcript and no methylation of RASSF1A promoter were found in explanted primary normal prostate epithelial and stromal cells. Complete silencing and methylation of RASSF1A promoter was observed in five widely used prostate carcinoma cell lines, which acquired the ability to grow in culture spontaneously, including LNCaP, PC-3, ND-1, DU-145, 22Rv1, and one primary prostate carcinoma immortalized by overexpression of the human telomerase catalytic subunit (RC-58T/hTERT). However, no silencing of RASSF1A was found in four other prostate carcinoma cell lines, which were adapted for cell culture after transformation with human papillomaviral DNA. Suppression of cell growth in vitro was demonstrated after the reintroduction of RASSF1A-expressing construct into LNCaP prostate carcinoma cells. Our data implicate the RASSF1A gene in human prostate tumorigenesis.
Kuzmin
Igor
I
Intramural Research Support Program, SAIC-Frederick, Inc., National Cancer Institute Frederick, Maryland 21702, USA. kuzmin@mail.ncifcrf.gov
Gillespie
John W
JW
Protopopov
Alexei
A
Geil
Laura
L
Dreijerink
Koen
K
Yang
Youfeng
Y
Vocke
Cathy D
CD
Duh
Fuh-Mei
FM
Zabarovsky
Eugene
E
Minna
John D
JD
Rhim
Johng S
JS
Emmert-Buck
Michael R
MR
Linehan
W Marston
WM
Lerman
Michael I
MI
D002455:Cell Division / Q000235:genetics; D002472:Cell Transformation, Viral; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D027383:Papillomaviridae / Q000502:physiology; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology; D019098:Telomerase / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D019098:Telomerase