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prosaposin ablation inactivates the MAPK and Akt signaling pathways and interferes with the development of the prostate gland

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Asian Journal of Andrology 2003年第1期5卷 57-63页

作者： Carlos R.Morales Haitham Badran Department of Anatomy and Cell Biology McGill University 3640 University Street Montreal Quebec Canada (H3A 2B2)Department of Anatomy and Cell Biology McGill University 3640 University Street Montreal Quebec Canada (H3A 2B2)

The recent development of a prosaposin -/- mouse model has allowed the investigation of the role of prosaposin in the development of the male reproductive organs. A morphometric analysis of the male reproductive system of 37 days old mice revealed that prosaposin ablation produced a 30 % reduction in size and weight of the testes, 37 % of the epididymis, 75 % of the seminal vesicles and 60 % of the prostate glands. Light microscopy (LM) showed that smaller testis size from homozygous mutant mice was associated with reduced spermiogenesis. Both, dorsal and ventral lobules of the prostate glands were underdeveloped in the homozygous mutant. LM analysis also showed that prostatic alveoli were considerably smaller and lined by shorter epithelial cells in the homozygous mutant. Smaller tubular diameter and shorter undifferentiated epithelial cells were also observed in seminal vesicles and epididymis. In the efferent ducts of the homozygous mutant mice, the epithelium was composed exclusively of ciliated cells in contrast to the heterozygotes, which showed the presence of nonciliated cells. Radioimmunoassays demonstrated that testosterone levels were normal or higher in mice with the inactivated prosaposin gene. Immunostaining of prostate sections with an anti-androgen receptor antibody showed that the epithelial cells lining the alveoli express androgen receptor in both the heterozygous and homozygous tissue. Similarly, sections immunostained with antibodies to the phosphorylated MAPKs and Akts strongly reacted with tall prostatic secretory cells in prostate from heterozygous mouse. On the other hand, the epithelial cells in the homozygous prostate remained unstained or weakly stained. These findings demonstrate that inactivation of the prosaposin gene affected the development of the prostate gland and some components of the MAPK pathway. 63 )

关键词： mouse prostate prosaposin mitogen activating phosphokinases (MAPKs)

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Expression and Significance of prosaposin (PSAP) in A Rat Model of Letrozole-induced Polycystic Ovary Syndrome

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Journal of Reproduction and Contraception 2013年第2期24卷 67-75页

作者： Yuan-yuan FANG Yi-ning LI Ying-xin YE Xiu-xia WANG Department of Gynaecology and Obstetrics Shengjing Hospital of China Medical University

Objective To investigate the prosaposin （PSAP） expression in polycystic ovaries. Methods The expression of PSAP was examined using immunohistochemistry, quantitative RT-PCR and Western blotting in a rat model with letrozole-induced polycystic ovary syndrom （PCOS）. Results Letrozole-induced PCOS rat models were similar to those in human PCOS in endocrine disturbances, metabolic characteristics and morphology features. And in these models both mRNA and protein levels of PSAP were significantly increased. Conclusion PSAP was overexpressed in the letrozole-induced PCOS rat model and might play an important role in the oceurance and development of PCOS.

关键词： polycystic ovary syndrom (PSAP) PCOS rat model (PCOS) androgen receptor (AR) prosaposin

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Identification of prosaposin as a Novel Interaction Partner for Rhox5

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Journal of Genetics and Genomics 2007年第5期34卷 392-399页

作者：郭芬黄晓锋李实骞孙丽敏李月琴李弘剑邹奕初彦辉周天鸿暨南大学生命科学技术学院牡丹江医学院黑龙江157011

prosaposin （Psap） has multiple cellular functions. It is involved in the development of the reproductive system, nervous system, and prostate cancer as well as in the regulation of sphingolipid catabolism by activating several lysosomal hydrolases involved in the metabolism of various sphingolipids. In this research, it was found to be a novel interaction partner for Rhox5 using yeast two-hybrid screening. The interaction between Rhox5 and the full-length prosapsoin （the transcript without exon 8） as well as the C-terminal domain of prosaposin, was further confirmed in both yeast two hybrid analysis and in vitro assay. It suggested that the C-terminal domain of prosaposin may be critical for the Rhox5-prosaposin interaction. Given the important roles played by both Rhox5 and prosaposin in maintaining the differentiation of male reproductive organs, spermatogenesis, and fertilization, the interaction between Rhox5 and prosaposin might regulate the development of male reproductive organs dynamically.

关键词： Rhox5 prosaposin functional interaction reproductive system

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Saposin C stimulates growth and invasion,activates p42/44 and SAPK/JNK signaling pathways of MAPK and upregulates uPA/uPAR expression in prostate cancer and stromal cells

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Asian Journal of Andrology 2005年第2期7卷 147-158,页

作者： Shahriar Koochekpour Oliver Sartor Masao Hiraiwa Tae-Jin Lee Walter Rayford Natascha Remmel Konrad Sandhoff ArdalanMinokadeh DavidY.Patten Department of Microbiology Immunology and Parasitology Stantey S.Scott Cancer Center Stanley S.Scott Cancer Center Department of Medicine Department of Neurosciences University of CaliforniaSan DiegoCenter for Molecular GeneticsLa JollaCalifornia 92093USA Department of Microbiology Immunology and Parasitology Stanley S.Scott Cancer Center Department of Urology Louisiana State University Health Sciences CenterNew OrleansLouisiana 70112USA Kekul■-Institut fuer Organische Chemie Und Biochemie Universitaet BonnD-53121 BonnGermany Department of Microbiology Immunology and Parasitology Stanley S.Scott Cancer Center

Aim:To determine the effect of saposin C (a known trophic domain of prosaposin) on proliferation,migration and invasion,as well as its effect on the expression of urokinase plasmonogen activator (uPA),its receptor (uPAR) and matrix metalloproteinases (MMP)-2 and -9 in normal and malignant prostate *** addition,we tested whether saposin C can activate p42/44 and stress-activated protein kinase/c-Jun NH_2-terminal kinase (SAPK/JNK) signal transduction pathways of the mitogen-activated protein kinase (MAPK) ***:We employed West- ern blot analysis,phospho-specific antibodies,cell proliferation assay,reverse transcriptase-polymerase chain reaction, in vitro kinase assays and migration and invasion to determine the effect of saposin C on various biological behaviors of prostate stromal and cancer ***:Saposin C,in a cell type-specific manner,upregulates uPA/uPAR and immediate early gene c-Jun expression,stimulates cell proliferation,migration and invasion and activates p42/44 and SAPK/JNK MAPK pathways in prostate stromal and cancer *** prostate epithelial cells were not responsive to saposin C treatment in the above ***:Saposin C functions as a multipotential modulator of diverse biological activities in prostate cancer and stromal *** results strongly suggest that saposin C functions as a potent growth factor for prostatic cells and may contribute to prostate carcinogenesis and/or the development of hormone-refractory prostate cancer.

关键词： saposin C prostate cancer uPA/uPAR prosaposin invasion growth factor SAPK/JNK MAPK MMP c-Jun

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