Amplification and overexpression of prosaposin in prostate cancer

Shahriar Koochekpour, Yujun Zhang, Rameen Beroukhim, Chia Ling Hsieh, Matthias D. Hofer, Haiyen E. Zhau, Masao Hiraiwa, Daniel Y. Pattan, Joy L. Ware, Ronald B. Luftig, Konrad Sandhoff, Charles L. Sawyers, Kenneth J. Pienta, Mark A. Rubin, Robert L. Vessella, William R. Sellers, Oliver Sartor

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43 引文 斯高帕斯(Scopus)

摘要

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 λTripIEx 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 Al 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, Al metastatic prostate cancer cell lines C4-2B and 1A8-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 over-expression in prostate cancer suggests, for the first time, a role for this molecule in the process of carcinogenesis or cancer progression in the prostate.
原文英語
頁(從 - 到)351-364
頁數14
期刊Genes Chromosomes and Cancer
44
發行號4
DOIs
出版狀態已發佈 - 十二月 2005
對外發佈

ASJC Scopus subject areas

  • 遺傳學
  • 癌症研究

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