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The JIMT-1 cell line is derived from a HER2-positive human breast carcinoma and is known for its resistance to trastuzumab, a commonly used HER2-targeted therapy. This makes JIMT-1 a valuable model for studying mechanisms of resistance to anti-HER2 treatments and for developing new therapeutic strategies. Unlike many other HER2-positive breast cancer cell lines, JIMT-1 mimics clinical cases where initial responses to HER2-targeted therapies are observed, but resistance subsequently develops. This feature has made it instrumental in exploring the efficacy of new drugs and combination therapies aimed at overcoming trastuzumab resistance.
JIMT-1 cells are also employed in studies investigating the interplay between HER2 and other signaling pathways, such as those involving the epidermal growth factor receptor (EGFR). Cross-talk between these pathways contributes to the cells' resistance to conventional therapies. Research has shown that JIMT-1 cells respond variably to different tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs). For example, while the cell line exhibits resistance to trastuzumab-emtansine (T-DM1) and shows only partial sensitivity to newer agents like trastuzumab-deruxtecan (T-DXd), it has been demonstrated that alternative ADCs such as disitamab vedotin (DV) might offer enhanced efficacy.
In vitro studies highlight the versatility of JIMT-1 for screening drugs that target not only HER2 but also other molecular pathways. These studies provide critical data for evaluating the synergistic effects of combination treatments involving ADCs and TKIs or novel targeted therapies. The cell line's behavior in various drug resistance scenarios underscores its importance in preclinical drug development, particularly for HER2-positive breast cancer with acquired or intrinsic resistance.
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- Oncogenes: HER-2 (insensitive to HER-2-inhibiting drugs, e.g. trastuzumab), ER-, PR-, AR-
- Mutational profile: Mutation: PIK3CA, p.Cys420Arg (c.1258T>C), heterozygous; Mutation: TP53, p.Arg248Trp (c.742C>T), homozygous
- cultureMedium: DMEM, w: 4.5 g/L Glucose, w: 4 mM L-Glutamine, w: 3.7 g/L NaHCO3, w: 1.0 mM Sodium pyruvate (Cytion article number 820300a)
- supplements: Supplement the medium with 10% heat-inactivated FBS
- dissociationReagent: Accutase
- subculturing: Remove the old medium from the adherent cells and wash them with PBS that lacks calcium and magnesium. For T25 flasks, use 3-5 ml of PBS, and for T75 flasks, use 5-10 ml. Then, cover the cells completely with Accutase, using 1-2 ml for T25 flasks and 2.5 ml for T75 flasks. Let the cells incubate at room temperature for 8-10 minutes to detach them. After incubation, gently mix the cells with 10 ml of medium to resuspend them, then centrifuge at 300xg for 3 minutes. Discard the supernatant, resuspend the cells in fresh medium, and transfer them into new flasks that already contain fresh medium.
- seedingDensity: 1 x 104 cells/cm2
- freezeMedium: As a cryopreservation medium, use complete growth medium (including FBS) + 10% DMSO for adequate post-thaw viability, or CM-1 (Cytion catalog number 800100), which includes optimized osmoprotectants and metabolic stabilizers to enhance recovery and reduce cryo-induced stress.
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