Illuminating offending proteins fluorescently

Fluorescence that illuminates a specific protein within a cell's nucleus may be a key to identifying cancer virulence and developing individualized treatment, according to researchers at Purdue University, West Lafayette, Ind.

Scientists created a technique that locates and maps proteins involved in regulating cell behavior automatically, notes Sophie Lelievre, assistant professor of basic medical sciences. The research results have, for the first time, made it possible to verify the distinction between multiplying cells that are harmless and those that are malignant.

Lelievre used human mammary cells to analyze nuclear protein distribution that shifted depending on whether a cell was malignant, had not yet developed a specific function, or was a normally functioning mature mammary cell.

"When you look at cells that don't yet have a specific function--aren't differentiated, compared to fully differentiated cells, which are now capable of functioning as breast cells--the organization of proteins in the nucleus varies tremendously," Lelievre explains. "Then, looking at how the proteins in malignant cells are distributed, it's a totally different pattern compared to normal differentiated cells."

Ultimately, scientists want to use the technique to determine not only if a lesion is malignant, but the exact type of cancer, how likely it is to spread, and the most appropriate treatment for a particular patient.

"The major problem exists in the premalignant stages of abnormal cells in determining whether cancer will develop, what type, and how invasive it will be," Lelievre emphasizes.

"The decision then is whether to treat or not to treat and how to proceed in these preliminary stages because only a certain percentage of these patients will ultimately develop cancer. We want to use this technique to identify subtypes of cells within lesions that potentially could become more aggressive forms of cancer."

The ability to see the protein patterns in the nucleus gives scientists one more tool in advancing the identification of types of cancer and appropriate treatment.

"We have genomics and proteomics that tell us about where genes are, whether they are functioning, and interactions of genes with proteins, but no one had focused on the changing distribution of nuclear proteins," Lelievre concludes. "Looking at the location of the proteins is a third part of studying cancer. We call it architectural proteomics because the proteins are still there but the location changes.

"In the case of malignant cells, the new technique may reveal what signaling process went awry to cause abnormal cell growth.

"It's as if, instead of losing an arm, your arm was placed in another location. It's abnormal, but you have everything you need--just not in the right place. It's what happens in cancer, too; the needed proteins are still there, but not in the right place anymore, so their function is altered."

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