Researchers at Lawrence Berkeley National Laboratory published a paper in October in the journal Cell Cycle detailing a novel method for creating immortal human mammary epithelial cells, the study of which may lead to more cancer treatment options.
The researchers were able to create cells with the characteristics necessary for immortality but without the numerous genomic errors that usually are a precursor to endless cell division. Immortality is usually the result of a long series of random mutations. This new cell line uses more targeted techniques to achieve immortality without the additional messy mutations, and it offers cancer researchers a cleaner slate from which to begin their investigations.
Martha Stampfer, a senior scientist at the Berkeley lab’s Stampfer Lab, said normal human cells eventually undergo senescence — meaning they stop dividing — when they reach a certain number of divisions or suffer environmental stress. Overcoming these barriers leads to immortal cells that often occurs as cancer becomes established.
“Human cells need to suppress immortality to suppress cancer,” Stampfer said.
There are at least two barriers that must be overcome to achieve cell immortality. The scientists knock out the p16 gene, which responds to stress by signaling senescence. They also activate an enzyme which replenishes telomeres — little caps that keep chromosomes from fraying at the ends.
The paper is the result of work in conjunction with scientists at the University of Arizona Cancer Center.
“The published model is very important for further study of human breast carcinogenesis,” said contributing investigator Lukas Vrba in an email. Vrba is a research associate in the Arizona lab, which is focused on breast cancer.
The Berkeley lab is supported by Department of Energy funding. In an email, Rick Borchelt, director of communications for DOE, said while the agency has no cancer research mandate, it does fund research about low-dose radiation. Part of that research involves cellular repair mechanisms, which are closely related to cancer studies.
A 1984 study by Stampfer led to commercialized immortal cells, but those cells suffered the additional mutations of previous technology. The new process avoids those random errors.
“When I started in the ’70s, I was fascinated,” Stampfer said. “All this stuff was just starting. Things have come full circle.”
Her initial investigation began when she became puzzled about why normal, noncancerous human cells are always mortal, yet rodent cells — such as those of lab mice — can be immortal. Mice, unlike humans, she said, do not live long enough in the wild to need protections from cancerous growth.
While humans have evolved mechanisms that try to stop erratic cell division, Stampfer said, mouse cells are immortal.
“Mice are all over out in nature, but eventually a hawk gets them — they die before cancer can develop,” she said.