Cancer growth stopped by normal gene

WASHINGTON — Researchers report showing that malignant growth is stopped by inserting a normal gene into test tube colonies of colon cancer cells, an experiment that could lead to finding natural proteins to switch off cancer.

In a study to be published Friday in the journal Science, scientists from the Johns Hopkins Oncology Center in Baltimore report that they have proven that a gene called p53 is able to prevent colon cancer tumors from growing in a laboratory culture.

P53 is one of a group of what is known as suppressor genes because they appear to act as a brake on cancer formation, said Suzanne Baker, a Hopkins cancer researcher. Suppressor genes have been found to be either missing or mutated in the cells of several types of solid cancer tumors, she said.

“What we assume is that the fact that a normal copy of the p53 gene is missing in the these cell is important in the formation of the cancer,” she said.

To test that idea, the researchers added the p53 gene to a colony of colon cancer cells growing in culture. The result, said Baker, is that the cancer growth “switched off.”

“If you put the normal copy (of the gene) back into these cells, the cells stop growing. They just won’t grow anymore,” she said.

Baker said inserting the normal p53 seems to re-establish the normal regulation of cell proliferation. The unregulated division of cells is a primary characteristic of cancer.

Researchers at Hopkins and at Case Western Reserve University in Cleveland also put the p53 into benign colon tumors and found that these tumors, which have the gene, were not affected. The researchers additionally put a mutated p53 gene into colon cancer cells colonies and found that the abnormal gene did not suppress the cell growth.

These experiments, said Baker, verified that it was the action of the normal gene that prevented the cancer from growing.

“This is a very important observation,” said Dr. Berton Zbar, a National Cancer Institute scientist. “The observation that you change the growth properties (of cancer cells) by inserting the normal gene is significant.”

“The concept demonstrated in this study is extremely important,” said Dr. John S. Macdonald, director of the Temple University Cancer Center in Philadelphia. “They have reached the genetic root of the problem of malignancy.”

Zbar and Macdonald said that p53 is missing or mutated in a several types of cancer — including brain, bone, breast and adrenal carcinoma — and that the Hopkins study may also apply to those cancers.

Other researchers, also working with laboratory cultures, proved earlier that restoring other suppressor genes can block growth of cancers of the eye and of the kidney. But the Hopkins study is the first to demonstrate the effect of a suppressor gene on one of the major cancer killers.