Researchers identify key protein's role in cancer development

August 30, 2013
Shuk-Mei Ho, PhD, is chair of UC's environmental health department.

Researchers at the University of Cincinnati (UC) have identified a key protein as the first dual-function co-regulator of an estrogen receptor that plays a crucial role in cancer development, opening the way to improved therapeutic targets for several types of cancer such as breast, prostate, lung and brain cancer.

The research was led by Shuk-Mei Ho, PhD, Jacob G. Schmidlapp Chair of Environmental Health and Professor at the UC College of Medicine and director of the Cincinnati Cancer Center, a collaborative initiative of UC, UC Health and Cincinnati Children's Hospital Medical Center. It was published online in the Journal of Biological Chemistry and will appear in the print edition of Aug. 30, 2013.

Ho and her team focused on the interactions between estrogen receptor beta (ER?1) and a co-regulator known as Tip60. Co-regulators are proteins that interact with , which are proteins that bind to specific DNA sequences. Co-regulators can be co-activators, which activate gene transcription, or co-repressors, which repress .

Unlike estrogen receptor alpha, which plays a role in initiation and progression, estrogen receptor beta is a potent tumor suppressor. Co-activating estrogen receptor beta would impair cell growth, thereby halting or slowing the development of cancer. Co-repressing estrogen receptor beta would promote cell growth and therefore encourage tumor development.

Using in vitro models, the team found that Tip60 served as both a co-activator and a co-repressor of estrogen receptor beta, depending on the DNA site involved. Specifically, it served as a co-activator at the binding site known as activation protein 1 (AP-1) but a co-repressor at the estrogen response element (ERE) site.

"For suppression of tumor growth—for example, in cancer treatment—the goal would be to bring Tip60 to estrogen receptor beta as a partnership with any genes that contain an AP-1 site," says Ho. "Therefore, we would want to design new drugs or identify natural products that accomplish this."

Ho notes that the drug fulvestrant, commonly used in the treatment of breast cancer, augments co-activation of Tip60 at the AP-1 site. Plant-derived products such as flax seed, soybeans and tofu contain phytoestrogens that also activate Tip60 at the AP-1 site.

Adds Yuet-Kin (Ricky) Leung, PhD, assistant professor of environmental health at UC and second author of the study, "The important thing to do is to figure out how we can actually bring either a repressor to estrogen receptor beta or an activator to it so cell death activity can be increased or decreased." (Promotion of cell growth, as opposed to the impairment of cell growth sought in tumor suppression, would be beneficial in such examples as wound healing or cardiovascular and brain injury repair, Leung notes.)

Explore further: Osteoporosis drug stops growth of breast cancer cells, even in resistant tumors

Related Stories

Osteoporosis drug stops growth of breast cancer cells, even in resistant tumors

June 15, 2013
A drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant to current targeted therapies, according to a Duke Cancer Institute ...

Estrogen enhancers tied to aggressive breast cancer

August 12, 2013
Adding to the picture of what prompts breast cancers to form, researchers from the Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center San Antonio today announced that "distant estrogen ...

UH researchers explore treatments for breast and colon cancers

August 22, 2011
University of Houston (UH) researchers have their sights set on developing possible treatments for breast and colon cancer.

New finding gives clues for overcoming tamoxifen-resistant breast cancer

November 2, 2012
(Medical Xpress)—A University of Cincinnati (UC) cancer biology team reports breakthrough findings about specific cellular mechanisms that may help overcome endocrine (hormone) therapy-resistance in patients with estrogen-positive ...

Study reveals new mechanism for estrogen suppression of liver lipid synthesis

May 23, 2013
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.

Spread of breast cancer linked to kisspeptins which normally inhibit metastasis

April 16, 2013
KISS 1 is a metastasis-suppressor gene which helps to prevent the spread of cancers, including melanoma, pancreatic and ovarian cancers to name a few. But new research from Western University's Schulich School of Medicine ...

Recommended for you

Study uncovers potential 'silver bullet' for preventing and treating colon cancer

July 26, 2017
In preclinical experiments, researchers at VCU Massey Cancer Center have uncovered a new way in which colon cancer develops, as well as a potential "silver bullet" for preventing and treating it. The findings may extend to ...

Compound shows promise in treating melanoma

July 26, 2017
While past attempts to treat melanoma failed to meet expectations, an international team of researchers are hopeful that a compound they tested on both mice and on human cells in a petri dish takes a positive step toward ...

Understanding cell segregation mechanisms that help prevent cancer spread

July 26, 2017
Scientists have uncovered how cells are kept in the right place as the body develops, which may shed light on what causes invasive cancer cells to migrate.

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.