Cell lines are populations of cells grown in a laboratory, originating from a single source and propagated over time. The MKN-45 cell line is a human cell line used in various research applications.
Origin and Key Features
The MKN-45 cell line was established from a human gastric adenocarcinoma, specifically from a poorly differentiated tumor. It originated from a liver metastasis in a 62-year-old Japanese female patient. The cell line was developed by H. Hojo.
MKN-45 cells exhibit characteristics typical of gastric cancer, including rapid growth and a degree of genetic instability. They are epithelial cells that primarily grow as adherent cells in culture, though some can also exist in suspension.
Genetically, MKN-45 cells possess several notable features. They express wild-type p53 protein, but also show a homozygous deletion of the p16CDKN2/MTS1/INK4A and p15MTS2 tumor suppressor genes. Furthermore, these cells are characterized by the amplification of the c-met oncogene and a promoter mutation in the E-cadherin gene, both of which are important in cancer progression.
Applications in Cancer Research
The MKN-45 cell line serves as a widely used model to investigate the biology of gastric tumors. Researchers frequently employ these cells for drug screening and the development of new therapeutic agents. This includes evaluating the effectiveness of various chemotherapy drugs, such as cisplatin, 5-fluorouracil, and docetaxel, as well as novel targeted therapies like monoclonal antibodies.
MKN-45 cells are also instrumental in understanding mechanisms of drug resistance. Additionally, these cells help elucidate the molecular pathways involved in gastric cancer progression, including the Wnt/β-catenin, PI3K/Akt, and MAPK/ERK pathways.
The ability of MKN-45 cells to form tumors when introduced into immunocompromised mice makes them suitable for in vivo studies, providing a model that mimics human disease more closely. This allows for the investigation of cancer progression, metastasis, and the effects of genetic modifications within a living system. Researchers can also study cancer stem cell properties, which are linked to tumor formation and recurrence.
Contributions to Understanding Disease
Research utilizing the MKN-45 cell line has significantly advanced the understanding of gastric cancer’s molecular underpinnings. Studies have elucidated molecular mechanisms driving the development and progression of the disease, such as the roles of signaling pathways like Wnt/β-catenin and PI3K/Akt. This detailed understanding helps in pinpointing vulnerabilities within cancer cells.
The cell line has been instrumental in identifying potential therapeutic targets for gastric cancer. For instance, the amplification of the c-met oncogene in MKN-45 cells has highlighted c-Met as a promising target for drug development. Furthermore, investigations into drug resistance using MKN-45 have provided insights into how cancer cells evade treatment, contributing to strategies for overcoming these resistances.
Insights gained from MKN-45 research have also shed light on cancer stem cell characteristics, which are thought to contribute to tumor initiation, spread, and relapse. Understanding these properties is important for developing therapies that can more effectively eliminate cancer cells. The findings from MKN-45 studies continually inform the development of new therapeutic strategies aimed at improving patient outcomes.