Immunogenicity and contraceptive potential of recombinant human sperm associated antigen (SPAG9)

Jagadish, Nirmala; Rana, Ritu; Mishra, Deepshikha; Garg, Manoj; Chaurasiya, Dipak; Hasegawa, Akiko; Koyama, Koji; Suri, Anil

doi:10.1016/j.jri.2005.06.004

Cited by 18 publications

(13 citation statements)

References 20 publications

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“…Our earlier studies have clearly shown that SPAG9 is highly immunogenic in vivo. Immunogenicity studies in rats showed the generation of antibodies against recombinant SPAG9 (8,24). Subsequently, SPAG9 DNA immunization studies in mice also showed specific immune response against SPAG9 (16).…”

Section: Discussionmentioning

confidence: 96%

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Garg

Chaurasiya

Rana

et al. 2007

Clinical Cancer Research

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Purpose: Cancer testis antigens are a group of tumor antigens with gene expression restricted to male germ cells in the testis and in various cancerous tissues. Recently, we reported a novel testisspecific sperm-associated antigen 9 (SPAG9) gene, a new member of the c-Jun NH 2 -terminal kinase^interacting protein family, having functional role in sperm-egg fusion and mitogenactivated protein kinase signaling pathway. National Center for Biotechnology Information Blast searches revealed SPAG9 nucleotide sequence similarities with expressed sequence tags of various cancerous tissues. In an effort to examine the clinical utility of SPAG9, we investigated the SPAG9 mRNA and protein expression in epithelial ovarian cancer (EOC). Humoral immune response to SPAG9 was also evaluated in EOC patients. Experimental Design: We determined the expression profile of SPAG9 transcript by reverse transcription-PCR and RNA in situ hybridization and SPAG9 protein expression by immunohistochemistry in EOC specimens and human ovarian cancer cell lines. Using ELISA and Western blotting, we analyzed specific antibodies for SPAG9 in sera from patients with EOC. Results: SPAG9 mRNA and protein expression was detected in 90% of EOC tissues and in all three human ovarian cancer cell lines. Specific SPAG9 antibodies were detected in 67% of EOC patients and not in sera from healthy individuals. Conclusions: Our findings indicate that SPAG9 is highly expressed in EOC and immunogenic in patients. Humoral immune response against SPAG9 in early stages of EOC suggests its important role in early diagnostics.These results collectively suggest that SPAG9, a novel member of cancer testis antigen family, could be a potential target for the development of diagnostic and therapeutic methods in EOC.

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Section: Discussionmentioning

confidence: 96%

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Garg

Chaurasiya

Rana

et al. 2007

Clinical Cancer Research

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“…The present investigation reports for the first time gene silencing of a sperm-specific protein using siRNA approach. SPAG9, a new member of JNK-interacting protein family, is a novel testis-specific protein exclusively expressed in testis [1,19]. The amino acid sequence analysis revealed conservation of SPAG9 in human and non-human primates predicting functional interactions of proteins, as well as the evolutionary relationships between genomes [2,[4][5][6]20].…”

Section: Discussionmentioning

confidence: 99%

Small interference RNA-mediated knockdown of sperm associated antigen 9 having structural homology with c-Jun N-terminal kinase-interacting protein

Rana

Jagadish

Garg

et al. 2006

Biochemical and Biophysical Research Communications

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Recently, we reported a novel testis-specific sperm associated antigen 9 (SPAG9) protein, a new member of the JNK-interacting protein family, having a functional role in sperm-egg fusion [N. Jagadish, R. Rana, R. Selvi, D. Mishra, M. Garg, S. Yadav, J.C. Herr, K. Okumura, A. Hasegawa, K. Koyama, A. Suri, Biochem. J. 389 (2005) 73-82]. NCBI Blast searches revealed SPAG9 nucleotide sequence similarities with ESTs of various cancerous tissues. In the present study, we compared the efficiency of two independent SPAG9 specific small interfering RNA (siRNA) constructs, BS/U6/spag9 and BS/U6/spag9-I, to ablate the SPAG9 expression in mammalian cells. A positive correlation between the ratio of target gene versus siRNA and the suppression of SPAG9 expression was observed. Further, the cotransfection of BS/U6/spag9 with pcDNA-SPAG9 and pFlag-CMV2-JNK-3 resulted in specific suppression of SPAG9 without affecting JNK-3 expression. The present investigation will eventually extend the application of SPAG9 siRNA in in vivo targeting experiments that aim to define the SPAG9 functional genomics in tumor and reproductive biology.

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“…In addition to these core molecules, several variants, that are the result of alternative splicing, have been isolated and characterized (18)(19)(20)(21)(22)(23)(24)(25)(26).…”

Section: Scaffold Proteins In the Jnk Pathwaymentioning

confidence: 99%

The role of scaffold proteins in JNK signalling

2009

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Immunogenicity and contraceptive potential of recombinant human sperm associated antigen (SPAG9)

Cited by 18 publications

References 20 publications

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer

Small interference RNA-mediated knockdown of sperm associated antigen 9 having structural homology with c-Jun N-terminal kinase-interacting protein

The role of scaffold proteins in JNK signalling

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