Featured Research

from universities, journals, and other organizations

Novel role of NEDD9 gene in early stages of breast cancer described

Date:
January 14, 2013
Source:
Fox Chase Cancer Center
Summary:
Breast cancer is the second leading cause of cancer deaths among women in the United States. Many of these deaths occur when there is an initial diagnosis of invasive or metastatic disease. A protein called NEDD9 has been linked to tumor invasion and metastasis in a variety of cancers. Researchers have now shown that NEDD9 plays a surprising role in the early stages of breast tumor development by controlling the growth of progenitor cells that give rise to tumors.

Breast cancer is the second leading cause of cancer deaths among women in the United States. Many of these deaths occur when there is an initial diagnosis of invasive or metastatic disease. A protein called NEDD9 -- which regulates cell migration, division and survival -- has been linked to tumor invasion and metastasis in a variety of cancers. Researchers at Fox Chase Cancer Center have now shown that NEDD9 plays a surprising role in the early stages of breast tumor development by controlling the growth of progenitor cells that give rise to tumors.

The findings, published in the journal Oncogene on January 14, 2013, could lead to personalized treatment strategies for women with breast cancer based on the levels of NEDD9 in their tumors.

"For several years, NEDD9 has been linked to tumor metastasis and invasion at later stages. This is the first study that really shows how important NEDD9 can be for the initiation of tumors in breast cancer, and to link this initiation process to progenitor cells," says lead study author Joy Little, PhD, a postdoctoral fellow at Fox Chase who works in the laboratory of senior study investigator Erica A. Golemis, PhD, Deputy Chief Scientific Officer and Vice President at Fox Chase.

In the study, Little, Golemis and their collaborators mated mice without the NEDD9 gene to mice engineered to develop HER2+ mammary tumors and unexpectedly found that these mice were largely resistant to tumor formation. Only 18% of the mice developed mammary tumors, compared with 80% of mice that had a functional NEDD9 gene. In contrast to previous research findings showing that an increase in NEDD9 levels promotes tumor aggressiveness, the researchers found that loss of NEDD9 had little effect on tumor metastasis, indicating that it is not required for this process in this specific context. Once formed, the tumors in mice lacking NEDD9 grew rapidly, suggesting that it either plays a less important role at later stages of tumor growth or tumors undergo compensatory changes that allow them to bypass the need for NEDD9.

Importantly, mice lacking NEDD9 showed a significant reduction in progenitor cell populations in the mammary gland compared with mice that had a functional NEDD9 gene. Progenitor cells from NEDD9-null mice were less likely to form three-dimensional mammospheres in culture, but proliferated at the same rate as cells from control mice. The loss of Nedd9 also made progenitor cells more sensitive to lower doses of two tumor-inhibiting drugs -- a Food and Drug Administration-approved Src inhibitor called dasatinib, and a focal adhesion kinase inhibitor from a class of drugs currently being tested in clinical trials for the treatment of cancer. These findings suggest that these types of drugs would more effectively control breast cancer tumors with low levels of NEDD9.

"Eventually, with a biopsy, you may be able to get a read-out of all the mutations that a tumor has, and each one would potentially dictate whether or not a certain line of therapy would work for a specific tumor," Little says. "If NEDD9 levels are higher in a particular tumor, we could potentially determine whether or not it would be more sensitive to specific inhibitors."

To follow up on this work, the researchers plan to determine the mechanisms by which NEDD9 controls tumor formation, and examine whether NEDD9 plays a similar role in early stages of other types of cancer.

Co-authors on the study include Victoria Serzhanova, Eugene Izumchenko, Brian L. Egleston, Andres J. Klein-Szanto, and Maria Shubina of Fox Chase; Erica Parise of the University of Pittsburgh; Grace Loudon of Bryn Mawr College; Sachiko Seo and Mineo Kurokawa of the University of Tokyo; and Michael F. Ochs of Johns Hopkins University.


Story Source:

The above story is based on materials provided by Fox Chase Cancer Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. J L Little, V Serzhanova, E Izumchenko, B L Egleston, E Parise, A J Klein-Szanto, G Loudon, M Shubina, S Seo, M Kurokawa, M F Ochs, E A Golemis. A requirement for Nedd9 in luminal progenitor cells prior to mammary tumorigenesis in MMTV-HER2/ErbB2 mice. Oncogene, 2013; DOI: 10.1038/onc.2012.607

Cite This Page:

Fox Chase Cancer Center. "Novel role of NEDD9 gene in early stages of breast cancer described." ScienceDaily. ScienceDaily, 14 January 2013. <www.sciencedaily.com/releases/2013/01/130114133355.htm>.
Fox Chase Cancer Center. (2013, January 14). Novel role of NEDD9 gene in early stages of breast cancer described. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2013/01/130114133355.htm
Fox Chase Cancer Center. "Novel role of NEDD9 gene in early stages of breast cancer described." ScienceDaily. www.sciencedaily.com/releases/2013/01/130114133355.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins