Discovery offers cancer prevention, diagnosis, treatment hopes

02/17/05

EAST LANSING, Mich. Michigan State University researchers have found that a certain gene, expressed within a human adult stem cell, could hold the key to not only offering new hope to cancer patients, but also to answering the question of how cancer originates.

The discovery that the gene known as oct-4 is expressed in normal adult stem cells, by MSU's James Trosko and colleagues, is detailed in the February issue of Carcinogenesis, one of the world's top cancer-research journals.

It was already known that the oct-4 gene was located in embryonic stem cells as well as tumor cells, but researchers were uncertain whether it was expressed in adult stem cells.

The MSU researchers, using methods pioneered in their laboratory, were able to test adult stem cells for the expression of the oct-4 gene and found that it was expressed in some adult stem cells.

"If oct-4 is a biomarker for adult stem cells that gives rise to cancer cells," Trosko said, "then learning how to turn off the expression of the oct-4 gene in cancer cells or even in pre-malignant cells should have tremendous implications for both prevention and treatment of cancer."

In particular, he said, the use of oct-4 as a screening marker to identify new chemoprevention dietary agents and chemotherapeutic drugs could be extremely helpful in fighting cancer.

"This is especially significant in light of recent findings that, within the billions of cells of a tumor, there exists a few 'cancer stem cells' that seem to be the cells that are resistant to cancer therapy," Trosko said. "In other words, current practices to treat cancers have been directed at the wrong tumor cells."

The oct-4 gene is a "regulatory" gene, one whose job is to control the expression of other genes.

When it comes to the question of where cancer cells originate, there are two prevailing theories: Either a single stem cell is the target for the process to begin, or any highly specialized, or "differentiated," cell can be the target cell.

The problem with the second theory, said Trosko, is that for a differentiated cell one that is already on its way to becoming a kidney cell or breast cell or any other specialized type of cell to become cancerous, it must first revert back to stem-cell stage.

"In other words," he said, "it has to turn back time.

"So what we found is that the human adult stem cell in which the oct-4 gene was expressed was the 'target' cell for the carcinogenic process to begin. In cells in which it was not expressed, they could not convert back to the adult stem cell stage and then go cancerous."

Trosko added that there are many benefits to working with adult stem cells, as opposed to embryonic stem cells.

"In particular, we're able to bypass the ethical, religious, legal and political issues that are raised when we talk about embryonic stem cells," he said. "We're able to get the adult stem cells from consenting adults."

Other members of Trosko's research team included Mei-Hui Tai, a visiting research associate in the Department of Pediatrics and Human Development; Chia-Cheng Chang, professor of pediatrics and human development; and Karl Olson, associate professor of physiology.

Source: Eurekalert & others

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