Amplification and overexpression of prosaposin in prostate cancer.
We identified prosaposin (PSAP) as a secreted protein expressed in androgen-independent (AI) prostate cancer cells by cloning/sequencing, after probing a PC-3 cDNA library expressed in the lambdaTriplEx phagemid expression vector with a polyclonal rabbit antibody generated against pooled human seminal plasma. PSAP is a neurotrophic molecule; its deficiency or inactivation has proved to be lethal in man and mice, and in mice, it leads to abnormal development and atrophy of the prostate gland, despite normal testosterone levels. We used Southern hybridization, quantitative real-time polymerase chain reaction, and/or single nucleotide polymorphism (SNP) array analysis, and we now report the genomic amplification of PSAP in the metastatic AI prostate cancer cell lines, PC-3, DU-145, MDA-PCa 2b, M-12, and NCI-H660. In addition, by using SNP arrays and a set of 25 punch biopsy samples of human prostate cancer xenografts (LAPC3, LuCaP 23.1, 35, 49, 58, 73, 77, 81, 86.2, 92.1, 93, 96, 105, and 115), lymph nodes, and visceral-organ metastases, we detected amplification of the PSAP locus (10q22.1) in LuCaP 58 and 96 xenografts and two lymph node metastases. In addition, AI metastatic prostate cancer cell lines C4-2B and IA8-ARCaP over-expressed PSAP mRNA without evidence of genomic amplification. Taken together with prior data that demonstrated the growth-, migration-, and invasion-promoting activities, the activation of multiple signal transduction pathways, and the antiapoptotic effect of PSAP (or one of its active domains, saposin C) in prostate cancer cells, our current observation of PSAP amplification or overexpression in prostate cancer suggests, for the first time, a role for this molecule in the process of carcinogenesis or cancer progression in the prostate.
Koochekpour
Shahriar
S
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. skooch@lsuhsc.edu
Zhuang
Yu-Jun
YJ
Beroukhim
Rameen
R
Hsieh
Chia-Ling
CL
Hofer
Matthias D
MD
Zhau
Haiyen E
HE
Hiraiwa
Masao
M
Pattan
Daniel Y
DY
Ware
Joy L
JL
Luftig
Ronald B
RB
Sandhoff
Konrad
K
Sawyers
Charles L
CL
Pienta
Kenneth J
KJ
Rubin
Mark A
MA
Vessella
Robert L
RL
Sellers
William R
WR
Sartor
Oliver
O
D015153:Blotting, Western; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049231:Saposins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
C483345:PSAP protein, human; D049231:Saposins