Second Look Acquits Gene Of Role In Breast Cancer

July 31, 1997

"This may just be another something the cancer cell messes up."

Johns Hopkins scientists studying a gene previously identified as a breast cancer gene report evidence that the gene may be innocent.

In a report in Cell last January, the TSG101 gene was identified as a tumor suppressor gene -- a gene that is often mutated or damaged in human breast cancers.

In this month's Cancer Research, the Hopkins team says TSG101 was consistently normal and undamaged in human breast cancer cells. The cells could not correctly "read" TSG101, but researchers said the same mistake occurs in normal cells and is unlikely to help create cancer.

"This may be just another something the cancer cell messes up," says Andrew Feinberg, M.D. "It definitely does not appear to be contributing to cancer cells' creation, but since this is the first time we've observed such an error in a cancer cell's ability to decipher a gene, we're not sure yet if it provides any advantages to the cancer cell."

With funding from the Department of Defense, Feinberg and Maxwell Lee, Ph.D., studied TSG101 in normal and cancerous human breast cells, and in other cells. They found no sign of deletions, mutations or other damage to TSG101 in any of the cells.

The cancer cells introduced mistakes into the gene's protein-building instructions, Feinberg says, but did so after "reading" the gene, which was not mutated.

"The cell encodes genetic instructions into a string of chemicals called ribonucleic acid or RNA, which later is used as a blueprint for building a protein," he explains. "But the string of RNA coding for the protein is normally interrupted at several points by coding that is not part of the protein. Before the cell can use it, it has to clip out these pieces. And it's in this splicing' process that something's going wrong in the cancerous cells."

In many cases, the cancerous cells cut too much out of the RNA, or pasted the remaining RNA together wrong. Normal and fetal cells made the same mistakes, but much less often.

"The earlier report of TSG101 deletions was actually detecting this altered splicing," says Feinberg.

"Is this important, this unusual splicing of RNA?" Feinberg asks. "It's possible. We think that a lot of what tumor cells do involves activating normal, specialized cell behaviors in an abnormal way, and this abnormal RNA splicing may be one example of that."
-end-


Johns Hopkins Medicine

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