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New method immortalizes cells and sheds light on cancer

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Researchers from the Lawrence Berkeley National Laboratory (CA, USA) have developed a new method that can create immortal human mammary epithelial cells. The results were recently published in the journal Cell Cycle.

The immortal human mammary epithelial cells created by the researchers exhibit normal genomes, unlike most human immortal cells, including tumor tissue cells. As a result, the cells could aid in the development of our understanding of the progression of cell immortalization as it naturally occurs in cancer.

Indefinite cell proliferation, which results in immortal cells, is an essential early step in the development of malignant tumors. However, the process of cell immortalization is still not well understood due to a lack of effective study methods. Up until now there has not been a tractable way to study cell immortalization as it occurs during cancer progression.

Research in mice has proven problematic in the past as rodent cells naturally express the enzyme required for immortality. The use of clonal cell lines of immortalized human cells and cell lines derived from tumors has also been difficult. These contain large numbers of mutations, which make it difficult to identify the errors responsible for pushing cells into immortality as opposed to errors that are secondary consequences of cancer development.

The Berkeley Lab researchers focused on cellular senescence in order to create a new method of studying immortalization in human cells. This natural process is believed to play an important role in cancer suppression.

In the study, the researchers bypassed cellular senescence by introducing molecular agents that are vital for cancer development into the cells. These molecular agents were able to target and overcome two tumor-fighting barriers that cause cells to become senescent.

One of these barriers, excessive cellular stress, was overcome by utilizing an agent that knocks out p16; a known tumor suppressor protein that stops the cell from proliferating.

The researchers also targeted telomeres in the cell that become shorter after each cell division. When the telomeres are too short to provide protection to the chromosomes, the cell stops dividing. The scientists overcame this by introducing c-Myc, a molecule that reactivates the enzyme that maintains telomeres, enabling cell division to continue.

Berkeley Lab scientist James Garbe commented: “It’s a very good model of a critical step in cancer progression.”

Using this reproducible procedure, immortal human epithelial cells were generated without any required genomic alterations to the cells.

Martha Stampfer, a fellow scientist in Berkeley Lab’s Life Sciences Division, commented: “Now that we have these immortal human mammary epithelial cells with normal genomes, we can study them to explore the molecular mechanisms behind cell immortality, from start to finish. We can also begin to think about ways to target this process therapeutically in order to prevent or reverse cancer progression.”

The method to develop immortal human mammary epithelial cells may represent the first breakthrough in understanding how cell immortalization could aid the fight against cancer.

Garbe continues: “We believe that research on these cells may stimulate new approaches for therapeutic intervention in cancer progression at the earliest stages.”

Source: Lawrence Berkeley National Laboratory press release

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