Biology:PRAME
 Generic protein structure example |
PRAME (preferentially expressed antigen of melanoma) is a protein that in humans is encoded by the PRAME gene.[1][2][3] Five alternatively spliced transcript variants encoding the same protein have been observed for this gene.[3]
Function
This gene encodes an antigen that is predominantly expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. This expression pattern is similar to that of other CT antigens, such as MAGE, BAGE and GAGE. However, unlike these other CT antigens, this gene is also expressed in acute leukemias. The overexpression of PRAME in tumor tissues and relative low levels in normal somatic tissues make it an attractive target for cancer therapy. In recent years, immunotherapy has spearheaded a new era of cancer therapy resulting in the development of numerous novel antigen-specific immunotherapy approaches. Studies on PRAME-specific immunotherapy primarily involve vaccines and cellular immunotherapies.[4]
PRAME can inhibit retinoic acid signaling and retinoic acid mediated differentiation and apoptosis.[5] PRAME overexpression in triple negative breast cancer has also been found to promote cancer cell motility through induction of the epithelial-to-mesenchymal transition.[6]
Model organisms
Model organisms have been used in the study of PRAME function. A conditional knockout mouse line called Prametm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13]
| Characteristic | Phenotype |
|---|---|
| All data available at.[8][13] | |
| Insulin | Normal |
| Homozygous viability at P14 | Normal |
| Homozygous Fertility | Normal |
| Body weight | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology 16 Weeks | Normal |
| Peripheral blood leukocytes 16 Weeks | Normal |
| Salmonella infection | Normal |
| Spleen Immunophenotyping | Normal |
| Mesenteric Lymph Node Immunophenotyping | Normal |
| Epidermal Immune Composition | Abnormal |
References
- ↑ "Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor". Immunity 6 (2): 199–208. Feb 1997. doi:10.1016/S1074-7613(00)80426-4. PMID 9047241.
- ↑ "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. Dec 1999. doi:10.1038/990031. PMID 10591208. Bibcode: 1999Natur.402..489D.
- ↑ 3.0 3.1 "Entrez Gene: PRAME preferentially expressed antigen in melanoma". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23532.
- ↑ "Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?". Cancers 11 (7): 984. July 2019. doi:10.3390/cancers11070984. PMID 31311081.
- ↑ "The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling". Cell 122 (6): 835–47. September 2005. doi:10.1016/j.cell.2005.07.003. PMID 16179254.
- ↑ "PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer". Journal of Translational Medicine 17 (1): 9. January 2019. doi:10.1186/s12967-018-1757-3. PMID 30602372.
- ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ 8.0 8.1 "International Mouse Phenotyping Consortium". http://www.mousephenotype.org/data/search?q=Prame#fq=*:*&facet=gene.
- ↑ "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. Jun 2011. doi:10.1038/nature10163. PMID 21677750.
- ↑ "Mouse library set to be knockout". Nature 474 (7351): 262–3. Jun 2011. doi:10.1038/474262a. PMID 21677718.
- ↑ "A mouse for all reasons". Cell 128 (1): 9–13. Jan 2007. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. Jul 2013. doi:10.1016/j.cell.2013.06.022. PMID 23870131.
- ↑ 13.0 13.1 "Infection and Immunity Immunophenotyping (3i) Consortium". http://www.immunophenotyping.org/data/search?keys=Prame&field_gene_construct_tid=All.
Further reading
- "Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?". Cancers 11 (7): 984. July 2019. doi:10.3390/cancers11070984. PMID 31311081.
- "PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer". Journal of Translational Medicine 17 (1): 9. January 2019. doi:10.1186/s12967-018-1757-3. PMID 30602372.
- "The immunogenic properties of melanoma-associated antigens recognized by cytotoxic T lymphocytes". Experimental and Clinical Immunogenetics 15 (1): 19–32. 1998. doi:10.1159/000019050. PMID 9619397.
- "Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies". Leukemia & Lymphoma 44 (3): 439–44. Mar 2003. doi:10.1080/1042819021000035725. PMID 12688312.
- "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. Sep 1996. doi:10.1101/gr.6.9.791. PMID 8889548.
- "Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth". Molecular Microbiology 27 (1): 171–86. Jan 1998. doi:10.1046/j.1365-2958.1998.00670.x. PMID 9466265.
- "Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies?". Cancer Research 58 (18): 4090–5. Sep 1998. PMID 9751617.
- "PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells". British Journal of Haematology 102 (5): 1376–9. Sep 1998. doi:10.1046/j.1365-2141.1998.00982.x. PMID 9753074.
- "Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene". FEBS Letters 466 (2–3): 367–71. Jan 2000. doi:10.1016/S0014-5793(00)01112-1. PMID 10682862.
- "The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells". European Journal of Immunology 30 (3): 803–9. Mar 2000. doi:10.1002/1521-4141(200003)30:3<803::AID-IMMU803>3.0.CO;2-P. PMID 10741395.
- "Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia". British Journal of Haematology 112 (4): 916–26. Mar 2001. doi:10.1046/j.1365-2141.2001.02670.x. PMID 11298586.
- "Clinical implications of PRAME gene expression in childhood acute myeloid leukemia". Cancer Genetics and Cytogenetics 133 (2): 118–23. Mar 2002. doi:10.1016/S0165-4608(01)00570-2. PMID 11943337.
- "PRAME gene expression in childhood acute lymphoblastic leukemia". Cancer Genetics and Cytogenetics 138 (1): 89–91. Oct 2002. doi:10.1016/S0165-4608(02)00582-4. PMID 12419593.
- "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics 83 (1): 153–67. Jan 2004. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
- "The tumor-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome". Clinical Cancer Research 10 (13): 4307–13. Jul 2004. doi:10.1158/1078-0432.CCR-03-0813. PMID 15240516.
- "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology 5 (10): R84. 2005. doi:10.1186/gb-2004-5-10-r84. PMID 15461802.
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