Navigation Links
A transcription factor called SLUG helps determines type of breast cancer
Date:5/2/2014

Findings and Significance: During breast-tissue development, a transcription factor called SLUG plays a role in regulating stem cell function and determines whether breast cells will mature into luminal or basal cells.

Studying factors, such as SLUG, that regulate stem-cell activity and breast-cell identity are important for understanding how breast tumors arise and develop into different subtypes. Ultimately, this knowledge may help the development of novel therapies targeted to specific breast-tumor subtypes.

Background: Stem cells are immature cells that can differentiate, or develop, into different cell types. Stem cells are important for replenishing cells in many tissues throughout the body. Defects that affect stem-cell activity can lead to cancer because mutations in these cells can cause uncontrollable growth. Some transcription factors regulate the differentiation or "programming" of breast stem cells into the more mature cells of the breast tissue. Abnormal expression of these transcription factors can change the normal programming of cells, which can lead to imbalances in cell types and the over-production of cells with enhanced properties of stem cells.

Breast tissue has two main types of cells: luminal cells and basal cells. Transcription factors, like SLUG, help control whether cells are programmed to become luminal cells or basal cells during normal breast development. In cancer, transcription factors can become deregulated, influencing what type of breast tumor will form. In aggressive basal-type breast tumors, SLUG is often over-expressed.

Previous work led by Charlotte Kuperwasser, principal investigator and senior author, determined that some common forms of breast cancer originate from luminal cells, whereas rare forms of breast cancer originate from basal cells. This difference in origins suggests that genes that affect the ability of a cell to become luminal or basal may also affect the formation of breast tumors. Because SLUG can regulate breast-cell differentiation, Kuperwasser's team investigated SLUG's role in breast-cell differentiation and tumor growth.

How the Study Was Conducted: The research team reduced the expression of the SLUG gene in human-derived breast cells and then used cell-sorting techniques to separate the cells into groups of luminal, basal, and stem cells. Next, they used mathematical modeling to measure the rate and frequency that each of the three cell types changed into another cell type. By comparing the rates between control cells and cells in which SLUG was reduced, the team was able to determine the role of SLUG in luminal-, basal-, and stem-cell transitions.

To test the result of their mathematical model, the research team examined and compared breast-tissue samples from mice in two groups: a control group with normal SLUG and an experimental group that did not express SLUG. Mammary glands from the experimental and control groups were analyzed for changes in structure, the amount and distribution of luminal and basal cells in the gland, and whether these cells had stem-cell activity.

Results: The SLUG-deficient mice exhibited defects in breast-cell differentiation. The mammary glands of these mice had too many luminal cells and defective basal cells that had luminal-cell characteristics. The control group of normal mice had a normal ratio of luminal to basal cells.

The SLUG-deficient mice showed defects in stem-cell function: Specifically, tumor formation and tissue regeneration was inhibited, an indication of defective stem cells, suggesting that SLUG was necessary to maintain normal luminal and basal cells within the mammary gland.

Additionally, SLUG-deficient cells when transplanted could not regenerate the mammary gland of the mouse, suggesting that SLUG is necessary for mammary stem-cell function. Tumor formation was also inhibited in SLUG-deficient mice, suggesting that SLUG may affect stem-cell activity necessary for tumor formation.

Discussion: First author Sarah Phillips, a Ph.D. student in genetics at the Sackler School of Graduate Biomedical Sciences at Tufts University:

"The study gives us insight into a potential source of cellular imbalance in breast tissues that can become cancerous. It also builds on the relationship between the levels of SLUG and the levels of cells that are associated with aggressive cancers. Breast cancer is very complex biologically, but any information we can find that could reduce this cellular over-growth could eventually be another tool to treat breast cancer at its sources."


'/>"/>

Contact: Siobhan Gallagher
siobhan.gallagher@tufts.edu
617-636-6586
Tufts University, Health Sciences Campus
Source:Eurekalert

Related biology news :

1. Study demonstrates cells can acquire new functions through transcriptional regulatory network
2. Transcription factor Lyl-1 critical in producing early T-cell progenitors
3. NIH backs Rice University study of delay in gene transcription networks
4. Stay-at-home transcription factor prevents neurodegeneration
5. FASEB SRC announces: Mechanism and Regulation of Prokaryotic Transcription Conference
6. Transcription factor may protect against hepatic injury caused by hepatitis C and alcohol
7. System-wide analyses have underestimated the importance of transcription in animals
8. Environmental factors in Tiny Tims near fatal illness
9. Soy-based S-equol supplement reduces metabolic syndrome risk factors
10. From scourge to saint: E. coli bacteria becomes a factory - to make cheaper, faster pharmaceuticals
11. Impaired recovery of Atlantic cod -- forage fish or other factors?
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/20/2017)... July 20, 2017 Delta (NYSE: DAL ) customers ... Delta aircraft at Reagan Washington National Airport (DCA). ... Delta launches biometrics to board aircraft ... Delta,s biometric boarding pass ... is now integrated into the boarding process to allow eligible Delta ...
(Date:5/16/2017)...  Veratad Technologies, LLC ( www.veratad.com ), an innovative ... verification solutions, announced today they will participate as a ... thru May 17, 2017, in Washington D.C.,s ... Identity impacts the lives of billions ... evolving digital world, defining identity is critical to nearly ...
(Date:4/18/2017)... , April 18, 2017  Socionext Inc., a global expert ... a media edge server, the M820, which features the company,s hybrid ... software provided by Tera Probe, Inc., will be showcased during the ... the NAB show at the Las Vegas ... ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... , ... October 12, 2017 , ... ... Vilnius, Lithuania, announced today that they have entered into a multiyear collaboration to ... provide CRISPR researchers with additional tools for gene editing across all applications. , ...
(Date:10/12/2017)... Irvine, ca (PRWEB) , ... October 12, 2017 ... ... for the Surgical Wound Market with the addition of its newest module, US ... the $1.2B market for thrombin hemostats, absorbable hemostats, fibrin sealants, synthetic sealants and ...
(Date:10/12/2017)... (PRWEB) , ... October 12, ... ... ) has launched Rosalindâ„¢, the first-ever genomics analysis platform specifically designed for ... complexity. Named in honor of pioneering researcher Rosalind Franklin, who made a ...
(Date:10/11/2017)... (PRWEB) , ... October 11, 2017 , ... ... any gene in its endogenous context, enabling overexpression experiments and avoiding the use ... with small RNA guides is transformative for performing systematic gain-of-function studies. , ...
Breaking Biology Technology: