Genomic Organization, Incidence, and Localization of the SPAN-X Family of Cancer-Testis Antigens in Melanoma Tumors and Cell Lines

Westbrook, V. Anne; Schoppee, Pamela D.; Diekman, Alan B.; Klotz, Kenneth L.; Allietta, Margaretta; Hogan, Kevin T.; Slingluff, Craig L.; Patterson, James W.; Frierson, Henry F.; Irvin, William P.; Flickinger, Charles J.; Coppola, Michael A.; Herr, John C.

doi:10.1158/1078-0432.ccr-0647-3

Cited by 52 publications

(69 citation statements)

References 41 publications

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“…It is interesting that this insertion presumably encodes a site of protein glycosylation. The presence of this site seems to be the reason that this protein is localized in the cytoplasm in contrast with other SPANXs (Westbrook et al 2004). The fact that the expansion of SPANX genes in recent evolution was initiated twice by the SPANX-B locus may be related to a high density of interspersed repeats in this region.…”

Section: Discussionmentioning

confidence: 94%

“…Alternatively, if SPANX genes are similar to other cancer/ testis-specific genes, they would be exclusively expressed in testis (Zendman et al 1999;Westbrook et al 2000;Wang et al 2003;Zendman et al 2003;Kouprina et al 2004;Salemi et al 2004;Scanlan et al 2004;Westbrook et al 2004). Thus, activation of any of these genes may result in malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…1). The SPANX (Sperm Protein Associated with the Nucleus on the X chromosome) multigene family encodes proteins whose expression is restricted to the normal testis, a few nongametogenic tissues, and certain tumors (Zendman et al 1999(Zendman et al , 2003Westbrook et al 2000Westbrook et al , 2004Goydos et al 2002;Wang et al 2003;Kouprina et al 2004). SPANX genes encode small unfolded proteins (∼100 amino acid residues), to some extent resembling the high mobility group A (HMGA) proteins involved in the formation of various nucleoprotein complexes.…”

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confidence: 99%

“…Similar to these proteins, SPANXs can form dimers and complexes with other proteins (Westbrook et al 2000(Westbrook et al , 2001. In transformed mammalian cells, SPANX proteins are associated with the nuclear envelope, a location similar to the one in human spermatozoa (Zendman et al 1999;Westbrook et al 2001Westbrook et al , 2004.…”

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confidence: 99%

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Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Kouprina¹,

Pavlı́ček²,

Noskov

et al. 2005

Genome Res.

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Genetic linkage studies indicate that germline variations in a gene or genes on chromosome Xq27-28 are implicated in prostate carcinogenesis. The linkage peak of prostate cancer overlies a region of ∼750 kb containing five SPANX genes (SPANX-A1, -A2, -B, -C, and -D) encoding sperm proteins associated with the nucleus; their expression was also detected in a variety of cancers. SPANX genes are >95% identical and reside within large segmental duplications (SDs) with a high level of similarity, which confounds mutational analysis of this gene family by routine PCR methods. In this work, we applied transformation-associated recombination cloning (TAR) in yeast to characterize individual SPANX genes from prostate cancer patients showing linkage to Xq27-28 and unaffected controls. Analysis of genomic TAR clones revealed a dynamic nature of the replicated region of linkage. Both frequent gene deletion/duplication and homology-based sequence transfer events were identified within the region and were presumably caused by recombinational interactions between SDs harboring the SPANX genes. These interactions contribute to diversity of the SPANX coding regions in humans. We speculate that the predisposition to prostate cancer in X-linked families is an example of a genomic disease caused by a specific architecture of the SPANX gene cluster.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Kouprina¹,

Pavlı́ček²,

Noskov

et al. 2005

Genome Res.

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“…A expressão dos genes CTs foi observada também em diversas linhagens de células derivada de tumores humanos (Yamada R et al, 2013). Quatro membros da família SPANX (A1, A2, B e D) foram descritos como expressos em tumores humanos, tais como melanomas, carcinomas de bexiga, mielomas e tumores hematopoiéticos (Wang Z et al, 2003;Westbrook VA et al, 2004;Salemi M et al, 2010). Resposta imune humoral e celular para proteínas codificadas pelos genes classificados como CTs têm sido observados em pacientes com doenças malignas, assim, os genes CTs são considerados alvos para a imunoterapia tumoral (Kouprina N et al, 2003;Almanzar G et al, 2009;Yamada R et al, 2013).…”

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Avaliação do transcriptoma e proteoma de células de câncer de mama com diferente perfil de expressão de SPARC (secreted protein acidic and rich in cysteine) na presença e ausência de docetaxel

Pavanelli¹

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Pavanelli AC. Transcriptome and proteome evaluation of breast cancer cells with different profile of SPARC expression (secreted protein acidic and rich in cysteine) in the presence and absence of docetaxelThe SPARC (secreted protein, acidic, cysteine-rich) gene encodes a 42kDa protein that belongs to a family of matricellular proteins, which interact with cell-surface receptors, growth factors and the ECM (extracellular matrix) components. SPARC plays a role in tissue remodeling, cell migration, angiogenesis, embryonic development, tumorigenesis and chemiosensitivity. Docetaxel, which is an antimicrotubulin agent, is an effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. The mechanisms of docetaxel resistance are poorly understood. In a previous study, we identified SPARC as differentially expressed in mammary epithelial cells expressing different levels of HER-2. In the present study, we evaluate the effects of SPARC overexpression on the sensitivity of breast cancer cells to docetaxel. MCF7 cells were transfected with the expression vector pCMV6-SPARC or pCMV6-Neo. Real time PCR, western blot and immunofluorescence were used to characterize the clones overexpressing SPARC. Proliferation was not significantly affected by SPARC overexpression. However, we observed an increased sensitivity to docetaxel when comparing the MCF7 control cells with the MCF7 cells overexpressing SPARC, indicating that SPARC expression has chemosensitive properties in breast cancer cells. We used cDNA microarray to evaluate the expression profile of MCF7 cells with SPARC overexpression in comparison with MCF7 control cells before and after docetaxel treatment for 24h.We have identified several differentially expressed genes potentially involved in SPARC-mediated chemosensibility to docetaxel. Seventy of the highly expressed genes were selected from all treatments and several molecular networks were identified using the Ingenuity Pathway Analysis (IPA). After manual annotation, six genes, SPANXA1, ALDH1A3, TPM4, TARP, XAF1, and WNT5A, potentially associated with SPARC mediated chemiosensitivity were selected and validated by qPCR. Using label-free approach for quantitative proteomic analysis, we further evaluated the proteomic changes in the comparison of the MCF7 cells control and over-expressing SPARC before and after docetaxel treatment. Among the molecular interaction networks, cytoskeleton remodeling pathway was the top pathway map observed in the comparison between MCF7 cells over-expressing SPARC and the control cells before docetaxel treatment and GTP metabolism pathway was the top pathway map observed in the comparison between MCF7 cells over-expressing SPARC and the control cells after docetaxel treatment. Transcriptome and proteome integrated data, resulted in forty commonly up and down regulated genes, being the WNT pathway represented among them. Our findings suggest that SPARC expression ca...

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Exclusion of the 750‐kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1‐linked families

Kouprina¹,

Lee²,

Pavlı́ček

et al. 2012

Genes Chromosomes & Cancer

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Several linkage studies provided evidence for the presence of the hereditary prostate cancer locus, HPCX1, at Xq27-q28. The strongest linkage peak of prostate cancer overlies a variable region of ~750 kb at Xq27 enriched by segmental duplications (SDs), suggesting that the predisposition to prostate cancer may be a genomic disorder caused by recombinational interaction between SDs. The large size of SDs and their sequence similarity make it difficult to examine this region for possible rearrangements using standard methods. To overcome this problem, direct isolation of a set of genomic segments by in vivo recombination in yeast (a TAR cloning technique) was used to perform a mutational analysis of the 750 kb region in X-linked families. We did not detect disease-specific rearrangements within this region. In addition, transcriptome and computational analyses were performed to search for non-annotated genes within the Xq27 region, which may be associated with genetic predisposition to prostate cancer. Two candidate genes were identified, one of which is a novel gene termed SPANXL that represents a highly diverged member of the SPANX gene family, and the previously described CDR1 gene that is expressed at a high level in both normal and malignant prostate cells, and mapped 210 kb of upstream the SPANX gene cluster. No disease-specific alterations were identified in these genes. To summarize, our results exclude the 750-kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy. Adjacent regions appear to be the most likely candidates to identify the elusive HPCX1 locus.

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Genomic Organization, Incidence, and Localization of the SPAN-X Family of Cancer-Testis Antigens in Melanoma Tumors and Cell Lines

Abstract: Conclusions: The data herein suggest that the SPAN-X protein may be a useful target in cancer immunotherapy.

Cited by 52 publications

References 41 publications

Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Avaliação do transcriptoma e proteoma de células de câncer de mama com diferente perfil de expressão de SPARC (secreted protein acidic and rich in cysteine) na presença e ausência de docetaxel

Exclusion of the 750‐kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1‐linked families

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