For the first time, researchers at Fred Hutchinson Cancer Research Center have identified and isolated¹ adult mammary（乳腺的） stem cells in mice. Long-term implications of this research may include the use of such cells to regenerate² breast tissue, provide a better understanding of the role of adult stem cells in breast cancer development, and develop potential new targets for anti-cancer drugs. The findings, by Larry Rohrschneider, Ph.D., a member of the Basic Sciences Division at the Hutchinson Center, and Lixia Bai, M.D., Ph.D., a research associate in his lab, are published in the Sept. 1 issue of Genes⁴ & Development.

Using a genetically⁵ modified mouse model, the researchers tagged stem cells with green fluorescent⁶（荧光的） protein (GFP), which exhibits bright green fluorescence during gene³ expression and can be easily seen under a microscope. GFP expression is controlled by the promoter of a newly identified gene, specifically expressed in stem cells, called s-SHIP.

“Until now, we have not been able to identify stem cells in mammary tissue. They have never been detected before with such specificity. It is extraordinary. You can see these green stem cells under the microscope in their pure, natural state,” said Rohrschneider, who has filed a patent（专利，执照） on the s-SHIP promoter-GFP-labeling technology.

Previous systems for isolating⁷ stem cells have relied on a variety of biomarkers, none of which have yielded a pure stem cell population. This limitation has prohibited accurate gene-expression analysis of such cells.

The researchers demonstrated the presence of active green stem cells at crucial stages of mammary development, such as puberty（青春期，开花期） and pregnancy⁸. During quiescent⁹ stages（静止期，休眠期） of development, however, the cells did not "light up."

Such stem cells represent a new alternative to induced pluripotent（多能的） stem cells, or genetically altered stem cells, for various medical applications.

For example, by isolating the pure green mammary cells from donor¹⁰ female transgenic mice, the researchers have demonstrated the regenerative ability of these cells by transplanting them into the mammary fat tissue of recipient¹¹ mice whose own mammary epithelium（上皮） has been removed.

"We have found that those transplanted green stem cells can generate new mammary tissue and this tissue can produce milk, just like normal mammary epithelial cells," said co-author Bai. "Identification of the exact stem cell and its location is the first critical and fundamental step toward understanding the regulatory mechanisms¹² of these important cells."

In addition to potential clinical applications regarding tissue regeneration, the researchers see these isolated stem cells as a window to better understanding how normal stem cells can become cancer stem cells, which are hypothesized（假定，猜测） to exist in tumors.

"Our belief right now is that perhaps the most aggressive tumors may be coming from the malignant¹⁴（恶性的） transformation¹⁵ of stem cells in healthy tissue," Rohrschneider said. "This new technology offers a unified¹⁶ model for identifying normal and cancer stem cells."

Cancer stem cells are thought to be responsible for tumor¹³ initiation¹⁷, growth, metastasis（转移，新陈代谢） , therapy resistance and disease relapse（复发） .

"Because stem cells are critical for both normal tissue development and cancer development, exploring how they are regulated in normal development will help us to better understand how they are transformed into breast cancer cells," Bai said. "By searching for new methods to effectively and specifically target cancer stem cells, we hope we can cure breast cancer someday." she said.