Human TP53 Knockout Cell Line-MOLM13
Cat.No. : CSC-RT2760
Host Cell: TP53 Target Gene: TP53
Size: 1x10^6 cells/vial, 1mL Validation: Sequencing
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Cell Line Information
Cell Culture Information
Safety and Packaging
| Cat. No. | CSC-RT2760 |
| Cell Line Information | This cell is a stable cell line with a homozygous knockout of human TP53 using CRISPR/Cas9. |
| Target Gene | TP53 |
| Host Cell | TP53 |
| Size Form | 1 vial (>10^6 cell/vial) |
| Shipping | Dry ice package |
| Storage | Liquid Nitrogen |
| Species | Human |
| Revival | Rapidly thaw cells in a 37°C water bath. Transfer contents into a tube containing pre-warmed media. Centrifuge cells and seed into a 25 cm2 flask containing pre-warmed media. |
| Mycoplasma | Negative |
| Format | One frozen vial containing millions of cells |
| Storage | Liquid nitrogen |
| Safety Considerations |
The following safety precautions should be observed. 1. Use pipette aids to prevent ingestion and keep aerosols down to a minimum. 2. No eating, drinking or smoking while handling the stable line. 3. Wash hands after handling the stable line and before leaving the lab. 4. Decontaminate work surface with disinfectant or 70% ethanol before and after working with stable cells. 5. All waste should be considered hazardous. 6. Dispose of all liquid waste after each experiment and treat with bleach. |
| Ship | Dry ice |
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Background
Case Study
Applications
The TP53 gene, also known as tumor protein p53, is one of the most important genes in cancer prevention. TP53 is located on the short arm of human chromosome 17 and plays a crucial role in regulating the cell cycle. The protein encoded by TP53 can directly bind to DNA and activate the transcription of genes responsible for DNA repair, cell cycle arrest, and apoptosis. In cases where DNA damage cannot be repaired, p53 can initiate apoptosis, a programmed cell death process, thereby preventing the proliferation of potential cancer cells. Due to these protective effects, TP53 has become the most commonly mutated gene in human cancer.
More than 50% of all human malignancies involve TP53 mutations, resulting in loss of p53 protein function, thereby increasing the risk of cancer development. Some non-mutation polymorphisms in TP53 have been studied in relation to cancer susceptibility, revealing a complex relationship between genotype and cancer risk. In addition, restoring p53 function in tumors is a promising therapeutic strategy, and several approaches are currently being studied to reactivate mutant p53 or enhance its pathways.
Resistance to cell death is a hallmark of cancer and a fundamental feature of acquired drug resistance. To maintain growth and survival, cancer cells often modulate cell death machinery by overexpressing anti-apoptotic BCL2 family members, including BCL2, BCL2L1, and MCL1. Venetoclax is an FDA-approved drug for the treatment of chronic lymphocytic leukemia (CLL) that has recently been approved for the treatment of acute myeloid leukemia (AML) in combination with hypomethylating agents. Here, we validated that inactivation of the TP53, BAX, and PMAIP1 genes results in resistance to venetoclax in AML cell lines. Resistance to venetoclax is due to an inability to execute apoptosis caused by loss of BAX, reduced BCL2 expression, and/or reliance on alternative BCL2 family members, such as BCL2L1. Resistance is accompanied by changes in mitochondrial homeostasis and cellular metabolism. Evaluation of the sensitivity of TP53 knockout cells to a panel of small molecule inhibitors revealed increased sensitivity to TRK inhibitors. These results suggest that TP53, the apoptotic network, and mitochondrial function are drivers of venetoclax response in AML and suggest strategies to overcome resistance.
NTRK receptors have recently gained attention for their oncogenic roles in multiple cancer types as components of fusion genes. In this study, to test whether NTRK transcripts are upregulated in TP53 knockout cells, the mRNA expression of NTRK1, NTRK2, and NTRK3 was assessed in MOLM-13 and MV4-11 cells with and without TP53 deletion. Although the expression levels of NTRK1 and NTRK2 were low in knockout cells, the expression level of NTRK3 RNA was high in TP53 knockout cells, indicating an upregulated transcriptional component of NTRK3 (Figure 1E). In control cells, the expression level of NTRK1 was low, explaining the sensitivity to entrectinib, while in TP53 knockout cells, the mRNA expression was switched to NTRK3. Analysis of TRK protein levels showed that the overall level and phosphorylation level of TRK proteins were increased in the presence of loss of p53 function. The researchers observed a significant decrease in TRK phosphorylation and downstream MAPK signaling after entrectinib treatment in TP53 knockout MOLM-13 cells, but not in control or parental cells (Figure 1F). Analysis of cell lysates obtained from AML patient samples showed a significant increase in TRK protein, with detectable levels of phosphorylated pan-TRK and TRKC in TP53 mutants but undetectable levels in WT cases (Figure 1G). In vitro analysis of leukemic blasts from these AML patients showed increased sensitivity to entrectinib in those samples carrying TP53 mutations.
Figure 1. Cells with loss-of-function alleles for TP53 or BAX have altered sensitivities to small-molecule inhibitors of various signaling pathways. (Nechiporuk T, et al., 2019)
TP53 knockout cell lines, such as the human TP53 knockout cell line - MOLM13, are valuable tools for a variety of research applications. These cell lines are characterized by the lack of the TP53 gene, a key tumor suppressor implicated in various cancers. Here are some of the applications of the human TP53 knockout cell line - MOLM13:
Cancer Research and Drug Development: TP53 mutations are present in many cancers. The MOLM13 TP53 knockout cell line enables researchers to study the direct effects of TP53 loss on cancer cell behavior. This is essential for understanding tumorigenesis, cancer progression, and identifying new therapeutic targets for drug development.
Functional Genomics: By comparing MOLM13 TP53 knockout cells to their wild-type counterparts, scientists can study the role of TP53 in different cellular processes, such as the cell cycle, apoptosis, and DNA repair mechanisms. This helps to elucidate the fundamental functions of TP53 in cell biology.
Genetic Disease Modeling: TP53 is absent in these cell lines, making them excellent models for studying genetic diseases associated with TP53 mutations. Researchers can examine molecular pathways that are altered by the lack of functional TP53.
Studying Mechanisms of Drug Resistance: TP53 knockout cell lines can be used to study how loss of TP53 leads to resistance to various chemotherapeutic drugs. Understanding these mechanisms is critical to developing strategies to overcome resistance to cancer treatments.
For research use only. Not intended for any clinical use.
