KRAS mutant-A375 Isogenic Cell Line
CRL-1619IG-1 ™
CRL-1619IG-1 ™
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Cells contain cytomegalovirus (CMV) DNA sequences
ATCC highly recommends that appropriate personal protective equipment is always used when handling vials. For cultures that require storage in liquid nitrogen, it is important to note that some vials may leak when submersed in liquid nitrogen and will slowly fill with liquid nitrogen. Upon thawing, the conversion of the liquid nitrogen back to its gas phase may result in the vial exploding or blowing off its cap with dangerous force creating flying debris. Unless necessary, ATCC recommends that these cultures be stored in the vapor phase of liquid nitrogen rather than submersed in liquid nitrogen.
Anti-cancer drug screening, BRAF drug resistant melanoma model, tumor-associated KRASG13D/BRAFV600E research, RAS-RAF kinase signaling pathway. Ideally the parental cell line (ATCC® CRL-1619™) is included as a control for drug-sensitive response in experiments with this cell line.
This is a malignant BRAFV600E/KRASG13D mutant isogenic line derived from the parental A375 (ATCC CRL-1619) cell line. The c.38G>A knock-in mutation encoding KRAS p.G13D protein expression was generated at ATCC by utilizing the CRISPR/Cas9 gene editing technology. This is a heterozygous mutation expressing the KRAS wild-type and the c. 38G>A mutant alleles.
BRAF is a proto-oncogene encoding B-RAF, a serine/threonine kinase of the RAF family that acts downstream of RAS and upstream of MEK in the MAPK/ERK signaling pathway. Mutations in BRAF lead to excessive cellular proliferation, differentiation, and survival. BRAF V600E mutations are present in 50% of melanomas and although there are current BRAF inhibitors used as successful therapeutics, patients often become resistant to drugs several months following treatment. One mechanism of resistance to these inhibitors is caused by upstream secondary RAS acquired mutations. The KRASG13D mutant isogenic line, ATCC CRL-1619IG-1 has been validated at the genomic, transcript, and protein bio-functional levels and exhibits significant resistance to the BRAF inhibitors Dabrafineb and Vemurafenib when compared to its parental cell line. CRL-1619IG-1 can be a useful model to study the RAS–RAF–MEK–ERK–MAP kinase signaling pathway and to screen potential BRAF inhibitors and anti-cancer compounds for drug discovery and development.
To ensure the highest level of viability, thaw the vial and initiate the culture as soon as possible upon receipt. If upon arrival, continued storage of the frozen culture is necessary, it should be stored in liquid nitrogen vapor phase and not at -70°C. Storage at -70°C will result in loss of viability.
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This material is subject to the following restrictions in addition to those outlined in the ATCC Material Transfer Agreement:
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Email: [email protected]
This material is subject to the following restrictions in addition to those outlined in the ATCC Material Transfer Agreement:
For information on obtaining additional rights, please contact:
ATCC Licensing
Email: [email protected]
Turner E, et al. CRISPR/Cas9 Edited RAS & MEK Mutant Cells Acquire BRAF and MEK Inhibitor Resistance with MEK1 Q56P Restoring Sensitivity to MEK/BRAF Inhibitor Combo and KRAS G13D Gaining Sensitivity to Immunotherapy. Cancers 14: 5449. 2022. PubMed: 36358868
Cormier JN, et al. Heterogeneous expression of melanoma-associated antigens and HLA-A2 in metastatic melanoma in vivo. Int. J. Cancer 75: 517-524, 1998. PubMed: 9466650
Sharma SD, et al. Melanotropic peptide-conjugated beads for microscopic visualization and characterization of melanoma melanotropin receptors. Proc. Natl. Acad. Sci. USA 93: 13715-13720, 1996. PubMed: 8943000
Gershwin ME, et al. Immunobiology of heterotransplanted human tumors in nude mice. J. Natl. Cancer Inst. 58: 1455-1463, 1977. PubMed: 857033
Giard DJ, et al. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J. Natl. Cancer Inst. 51: 1417-1423, 1973. PubMed: 4357758