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Your search keyword '"Perez-Mancera, Pedro A."' showing total 16 results
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16 results on '"Perez-Mancera, Pedro A."'

5. The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma

Author

Perez-Mancera, Pedro A., Rust, Alistair G., van der Weyden, Louise, Kristiansen, Glen, Li, Allen, Sarver, Aaron L., Silverstein, Kevin A.T., Grutzmann, Robert, Aust, Daniela, Rummele, Petra, Knosel, Thomas, Herd, Colin, Stemple, Derek L., Kettleborough, Ross, Brosnan, Jacqueline A., Li, Ang, Morgan, Richard, Knight, Spencer, Yu, Jun, Stegeman, Shane, Collier, Lara S., ten Hoeve, Jelle J., de Ridder, Jeroen, Klein, Alison P., Goggins, Michael, Hruban, Ralph H., Chang, David K., Biankin, Andrew V., Grimmond, Sean M., Wessels, Lodewyk F.A., Wood, Stephen A., Iacobuzio-Donahue, Christine A., Pilarsky, Christian, Largaespada, David A., Adams, David J., and Tuveson, David A.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations (1-4) in addition to numerous lower frequency genetic events of uncertain significance (5). Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis (6,7) in a mouse model of pancreatic ductal preneoplasia (8) to identify genes that cooperate with oncogenic [Kras.sup.G12D] to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia (9), we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2'-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with [Kras.sup.G12D] to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA., The biological sequelae of PDA has been partially attributed to frequent and well characterized mutations in KRAS (>90%), CDKN2A (>90%), TP53 (70%) and SMAD4 (55%) (1-4). Recent genomewide analyses have [...]

Published
2012
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7. Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry

Author

Sage, Julien, Miller, Abigail L., Perez-Mancera, Pedro A., Wysocki, Julianne M., and Jacks, Tyler

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Julien Sage [1]; Abigail L. Miller [1]; Pedro A. Pérez-Mancera [3]; Julianne M. Wysocki [1]; Tyler Jacks (corresponding author) [1, 2] Cancer cells arise from normal cells through the [...]

Published
2003
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8. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Author

Biankin, Andrew V., Waddell, Nicola, Kassahn, Karin S., Gingras, Marie-Claude, Muthuswamy, Lakshmi B., Johns, Amber L., Miller, David K., Wilson, Peter J., Patch, Ann-Marie, Wu, Jianmin, Chang, David K., Cowley, Mark J., Gardiner, Brooke B., Song, Sarah, Harliwong, Ivon, Idrisoglu, Senel, Nourse, Craig, Nourbakhsh, Ehsan, Manning, Suzanne, Wani, Shivangi, Gongora, Milena, Pajic, Marina, Scarlett, Christopher J., Gill, Anthony J., Pinho, Andreia V., Rooman, Ilse, Anderson, Matthew, Holmes, Oliver, Leonard, Conrad, Taylor, Darrin, Wood, Scott, Xu, Qinying, Nones, Katia, Lynn Fink, J., Christ, Angelika, Bruxner, Tim, Cloonan, Nicole, Kolle, Gabriel, Newell, Felicity, Pinese, Mark, Scott Mead, R., Humphris, Jeremy L., Kaplan, Warren, Jones, Marc D., Colvin, Emily K., Nagrial, Adnan M., Humphrey, Emily S., Chou, Angela, Chin, Venessa T., Chantrill, Lorraine A., Mawson, Amanda, Samra, Jaswinder S., Kench, James G., Lovell, Jessica A., Daly, Roger J., Merrett, Neil D., Toon, Christopher, Epari, Krishna, Nguyen, Nam Q., Barbour, Andrew, Zeps, Nikolajs, Brancato, Mary-Anne L., Rowe, Sarah J., Simpson, Skye L., Martyn-Smith, Mona, Thomas, Michelle T., Pettit, Jessica, Tao, Jiang, DiPietro, Renee, Watson, Clare, Wong, Rachel, Giry-Laterriere, Marc, Pavlakis, Nick, Guminski, Alex, Asghari, Ray, Pavey, Darren A., Das, Amitabha, Cosman, Peter H., Ismail, Kasim, O’Connor, Chelsie, Lam, Vincent W., McLeod, Duncan, Pleass, Henry C., Richardson, Arthur, James, Virginia, Cooper, Caroline L., Joseph, David, Sandroussi, Charbel, Crawford, Michael, Gallagher, James, Texler, Michael, Forrest, Cindy, Laycock, Andrew, Epari, Krishna P., Ballal, Mo, Fletcher, David R., Mukhedkar, Sanjay, Spry, Nigel A., DeBoer, Bastiaan, Chai, Ming, Beilin, Maria, Feeney, Kynan, Ruszkiewicz, Andrew R., Worthley, Chris, Tan, Chuan P., Debrencini, Tamara, Chen, John, Brooke-Smith, Mark E., Papangelis, Virginia, Tang, Henry, Barbour, Andrew P., Clouston, Andrew D., Martin, Patrick, O’Rourke, Thomas J., Chiang, Amy, Fawcett, Jonathan W., Slater, Kellee, Yeung, Shinn, Hatzifotis, Michael, Hodgkinson, Peter, Christophi, Christopher, Nikfarjam, Mehrdad, Mountain Victorian Cancer Biobank, Angela, Eshleman, James R., Schulick, Richard D., Wolfgang, Christopher L., Morgan, Richard A., Hodgin, Mary B., Lawlor, Rita T., Capelli, Paola, Beghelli, Stefania, Corbo, Vincenzo, Scardoni, Maria, Pederzoli, Paolo, Tortora, Giampaolo, Bassi, Claudio, Kakkar, Nipun, Zhao, Fengmei, Qing Wu, Yuan, Wang, Min, Muzny, Donna M., Fisher, William E., Charles Brunicardi, F., Hodges, Sally E., Reid, Jeffrey G., Drummond, Jennifer, Chang, Kyle, Han, Yi, Lewis, Lora R., Dinh, Huyen, Buhay, Christian J., Beck, Timothy, Timms, Lee, Sam, Michelle, Begley, Kimberly, Brown, Andrew, Pai, Deepa, Panchal, Ami, Buchner, Nicholas, De Borja, Richard, Denroche, Robert E., Yung, Christina K., Serra, Stefano, Onetto, Nicole, Mukhopadhyay, Debabrata, Tsao, Ming-Sound, Shaw, Patricia A., Petersen, Gloria M., Gallinger, Steven, Hruban, Ralph H., Maitra, Anirban, Iacobuzio-Donahue, Christine A., Tempero, Margaret A., Mann, Karen M., Jenkins, Nancy A., Perez-Mancera, Pedro A., Adams, David J., Largaespada, David A., Wessels, Lodewyk F. A., Rust, Alistair G., Stein, Lincoln D., Tuveson, David A., Copeland, Neal G., Musgrove, Elizabeth A., Scarpa, Aldo, Hudson, Thomas J., Sutherland, Robert L., Wheeler, David A., Pearson, John V., McPherson, John D., Gibbs, Richard A., and Grimmond, Sean M.

Published
2012
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9. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium

Author

Holland, Daniel G., Burleigh, Angela, Git, Anna, Goldgraben, Mae A., Perez-Mancera, Pedro A., Chin, Suet-Feung, Hurtado, Antonio, Bruna, Alejandra, Ali, Raza H., Greenwood, Wendy, Dunning, Mark J., Samarajiwa, Shamith, Menon, Suraj, Rueda, Oscar M., Lynch, Andy G., McKinney, Steven, Ellis, Ian O., Eaves, Connie J., Carroll, Jason S., Curtis, Christina, Aparicio, Samuel, and Caldas, Carlos

Published
2011
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10. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma

Author

Varela, Ignacio, Tarpey, Patrick, Raine, Keiran, Huang, Dachuan, Ong, Choon Kiat, Stephens, Philip, Davies, Helen, Jones, David, Lin, Meng-Lay, Teague, Jon, Bignell, Graham, Butler, Adam, Cho, Juok, Dalgliesh, Gillian L., Galappaththige, Danushka, Greenman, Chris, Hardy, Claire, Jia, Mingming, Latimer, Calli, Lau, King Wai, Marshall, John, McLaren, Stuart, Menzies, Andrew, Mudie, Laura, Stebbings, Lucy, Largaespada, David A., Wessels, L. F. A., Richard, Stephane, Kahnoski, Richard J., Anema, John, Tuveson, David A., Perez-Mancera, Pedro A., Mustonen, Ville, Fischer, Andrej, Adams, David J., Rust, Alistair, Chan-on, Waraporn, Subimerb, Chutima, Dykema, Karl, Furge, Kyle, Campbell, Peter J., Teh, Bin Tean, Stratton, Michael R., and Futreal, Andrew P.

Published
2011
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11. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia.

Author

Pearson, Helen B., Perez-Mancera, Pedro A., Dow, Lukas E., Ryan, Andrew, Tennstedt, Pierre, Bogani, Debora, Elsum, Imogen, Greenfield, Andy, Tuveson, David A., Simon, Ronald, and Humbert, Patrick O.

Subjects
*PROSTATE cancer, *PROTEIN deficiency, *LABORATORY mice, *EPITHELIAL cells, *MITOGEN-activated protein kinases, *GUANOSINE triphosphatase, *CARCINOGENESIS
Abstract

Loss of cellular polarity is a hallmark of epithelial cancers, raising the possibility that regulators of polarity have a role in suppressing tumorigenesis. The Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity. In human colorectal, breast, and endometrial cancers, expression of the Scribble complex member SCRIB is often mislocalized and deregulated. Here, we report that Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis revealed that prostate-specific loss of Scrib in mice combined with expression of an oncogenic Kras mutation promoted the progression of prostate cancer that recapitulated the human disease. The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer. These data suggest that the polarity network could provide a new avenue for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Published
2011
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12. The radioresistance biological function of the SCF/kit signaling pathway is mediated by the zinc-finger transcription factor Slug.

Author

Perez-Losada, Jesus, Sanchez-Martin, Manuel, Perez-Caro, Maria, Perez-Mancera, Pedro A, and Sanchez-Garcia, Isidro

Subjects
ZINC-finger proteins, TRANSCRIPTION factors, HEMATOPOIESIS, STEM cells, CELLULAR signal transduction
Abstract

Radiation-induced destruction of the hematopoietic system is the primary cause of death based on the findings that transfer of normal bone marrow cells prevents death from lethal irradiation. The stem cell factor-c-kit signaling pathway (SCF/c-kit) has been previously implicated in the hematopoietic recovery which prevents death from lethal irradiation, but the molecular mechanisms that mediate this biological effect are unknown. Since mutations on SCF, c-kit and Slug genes have a similar phenotype in mice, we examined if Slug could complement the radiosensitivity of kit-deficient mice. In this report, we show that Slug acts as a radioprotection agent as lack of Slug results in increased radiosensitivity. This effect cannot be recovered by activating SCF/c-kit in lethally irradiated Slug-deficient mice, as SCF-treated mice did not demonstrate stimulation of hematopoietic recovery leading to survival of the Slug-deficient mice. We found that we could complement the hematopoietic failure in lethally irradiated c-kit-deficient mice by transducing them with a TAT-Slug protein. We conclude that the zinc-finger transcription factor Slug is absolutely necessary for survival from lethal irradiation and identify Slug as the molecular target that mediates the radioprotection through SCF/c-kit. These results indicate that Slug may be a molecular component conferring radioresistance to cancer cells.Oncogene (2003) 22, 4205-4211. doi:10.1038/sj.onc.1206467 [ABSTRACT FROM AUTHOR]

Published
2003
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13. Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice.

Author

Perez-Mancera, Pedro Antonio, Perez-Losada, Jesus, Sanchez-Martin, Manuel, Rodriguez-Garcia, Maria Aranzazu, Flores, Teresa, Battaner, Enrique, Guttierez-Adan, Alfonso, Pintado, Belen, and Sanchez-Garcia, Isidro

Subjects
*PROTEINS, *LIPOSARCOMA, *MESENCHYME tumors
Abstract

Presents a study that examined the role of the expression of FUS domain in the restoration of liposarcoma development in CHOP-transgenic mice. Components of mesenchymal cancer development; Characteristics of liposarcoma; Information on the FUS-CHOP fusion; Functions of the FUS component of the fusion protein.

Published
2002
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14. PDAC-associated fibroblasts are less responsive to an anti-fibrotic stimulus and more responsive to a positive regulator of fibroblast activation than normal activated fibroblasts.

Author

Barrera, Lawrence N., Evans, Anthony, Lane, Brian, Brumskill, Sarah, Oldfield, Frances, Campbell, Fioana, Andrews, Timothy, Lu, Zipeng, Perez-Mancera, Pedro A., Liloglou, Triantafillos, Jalali, Mehdi, Dawson, Rebecca, Nunes, Quentin, Phillips, Phoebe, Timms, John F., Menon, Usha, Halloran, Christopher, Greenhalf, William, Neoptolemos, John P., and Costello, Eithne

Published
2019
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16. In Vivo Identification of Tumor- Suppressive PTEN ceRNAs in an Oncogenic BRAF-Induced Mouse Model of Melanoma

Author

Karreth, Florian A., Tay, Yvonne, Perna, Daniele, Ala, Ugo, Tan, Shen Mynn, Rust, Alistair G., DeNicola, Gina, Webster, Kaitlyn A., Weiss, Dror, Perez-Mancera, Pedro A., Krauthammer, Michael, Halaban, Ruth, Provero, Paolo, Adams, David J., Tuveson, David A., and Pandolfi, Pier Paolo

Subjects
*TUMOR suppressor proteins, *ONCOGENES, *MELANOMA, *NON-coding RNA, *GENETIC regulation, *GENETIC transcription, *MUTAGENESIS, *LABORATORY mice
Abstract

Summary: We recently proposed that competitive endogenous RNAs (ceRNAs) sequester microRNAs to regulate mRNA transcripts containing common microRNA recognition elements (MREs). However, the functional role of ceRNAs in cancer remains unknown. Loss of PTEN, a tumor suppressor regulated by ceRNA activity, frequently occurs in melanoma. Here, we report the discovery of significant enrichment of putative PTEN ceRNAs among genes whose loss accelerates tumorigenesis following Sleeping Beauty insertional mutagenesis in a mouse model of melanoma. We validated several putative PTEN ceRNAs and further characterized one, the ZEB2 transcript. We show that ZEB2 modulates PTEN protein levels in a microRNA-dependent, protein coding-independent manner. Attenuation of ZEB2 expression activates the PI3K/AKT pathway, enhances cell transformation, and commonly occurs in human melanomas and other cancers expressing low PTEN levels. Our study genetically identifies multiple putative microRNA decoys for PTEN, validates ZEB2 mRNA as a bona fide PTEN ceRNA, and demonstrates that abrogated ZEB2 expression cooperates with BRAFV600E to promote melanomagenesis. [ABSTRACT FROM AUTHOR]

Published
2011
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