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A431 cells

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A431 cells are a model human cell line (epidermoid carcinoma) used in biomedical research.[1]

Characteristics

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A431 cells were established from an epidermoid carcinoma in the skin (epidermis) of an 85- year-old female patient. Epidermal growth factor (EGF) stimulation of A431 cells induces rapid tyrosine phosphorylation of intracellular signaling proteins which control cellular processes such as growth, proliferation and apoptosis. At low (picomolar) concentrations, EGF promotes cell growth of A431 cells whereas at higher (nanomolar) concentrations it inhibits growth by causing the cells to terminally differentiate. Treatment of A431 cells with bradykinin reduces basal and EGF-induced EGFR phosphorylation.[2] Treatment with Sertoli cell secreted growth factor (SCSGF) strongly induces cell proliferation.[3][4] Stimulation of A431 cells with phorbol esters induces expression of interleukin 1-related protein IL1H.

Research Applications

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A431 cells are used in studies of the cell cycle and cancer-associated cell signalling pathways since they express abnormally high levels of the Epidermal growth factor receptor (EGFR). They are often used as a positive control for EGFR expression. They contain no functional p53, a potent tumor suppressor gene, and are highly sensitive to mitogenic stimuli. In xenografts, A431 cells have shown antitumorigenic properties of introduced EGF and related radiation sensitization characteristics. Other in vitro studies have found EGF to also cause substantial lowering of DNA replication and protein synthesis.[5] The A431 lines engineered to express tumor antigens such as mesothelin[6] and GPC3[7] have been made as cell models to test cancer therapeutics.

References

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  1. ^ "A431 - Cytokines and Cells Online Pathfinder Encyclopaedia".
  2. ^ Graness A, Hanke S, Boehmer FD, Presek P, Liebmann C (April 2000). "Protein-tyrosine-phosphatase-mediated epidermal growth factor (EGF) receptor transinactivation and EGF receptor-independent stimulation of mitogen-activated protein kinase by bradykinin in A431 cells". The Biochemical Journal. 347 (Pt 2): 441–7. doi:10.1042/0264-6021:3470441. PMC 1220976. PMID 10749673.
  3. ^ Buch JP, Lamb DJ, Lipshultz LI, Smith RG (April 1988). "Partial characterization of a unique growth factor secreted by human Sertoli cells". Fertility and Sterility. 49 (4): 658–65. doi:10.1016/S0015-0282(16)59836-7. PMID 3350161.
  4. ^ Lamb DJ, Spotts GS, Shubhada S, Baker KR (August 1991). "Partial characterization of a unique mitogenic activity secreted by rat Sertoli cells". Molecular and Cellular Endocrinology. 79 (1–3): 1–12. doi:10.1016/0303-7207(91)90089-B. PMID 1936536. S2CID 23996107.
  5. ^ MacLeod CL, Luk A, Castagnola J, Cronin M, Mendelsohn J (April 1986). "EGF induces cell cycle arrest of A431 human epidermoid carcinoma cells". Journal of Cellular Physiology. 127 (1): 175–82. doi:10.1002/jcp.1041270121. PMID 3007537. S2CID 19448225.
  6. ^ Ho M, Hassan R, Zhang J, Wang QC, Onda M, Bera T, Pastan I (May 2005). "Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients". Clinical Cancer Research. 11 (10): 3814–20. doi:10.1158/1078-0432.CCR-04-2304. PMID 15897581.
  7. ^ Phung Y, Gao W, Man YG, Nagata S, Ho M (September 2012). "High-affinity monoclonal antibodies to cell surface tumor antigen glypican-3 generated through a combination of peptide immunization and flow cytometry screening". mAbs. 4 (5): 592–9. doi:10.4161/mabs.20933. PMC 3499300. PMID 22820551.
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