Featured Research

from universities, journals, and other organizations

Mutation In PTEN Gene Can Cause Cancer And Autoimmune Disease

Date:
September 27, 1999
Source:
Memorial Sloan-Kettering Cancer Center
Summary:
Although it has been known that a mutation in both copies of the PTEN tumor suppressor gene impairs a cell's ability to program its death, researchers have found that losing function of only one of the pair is enough to disrupt this vital signaling mechanism. Their findings, published in the September 24 issue of the journal Science, show that inactivation of just one PTEN gene allows some white blood cells to accumulate unchecked and "attack" their own organs.

New York, September 23 - Although it has been known that a mutation in both copies of the PTEN tumor suppressor gene impairs a cell's ability to program its death, researchers have found that losing function of only one of the pair is enough to disrupt this vital signaling mechanism. Their findings, published in the September 24 issue of the journal Science, show that inactivation of just one PTEN gene allows some white blood cells to accumulate unchecked and "attack" their own organs. This process, studied in mice, eventually results in the development of chronic fatal conditions that may include cancer and an autoimmune disease.

"The mutation of the PTEN gene is clearly linked with the cell's inability to die -- a process called apoptosis. As a result of our research, we have seen that it is the gene most highly implicated in malignant tumors," said Pier Paolo Pandolfi, M.D., Ph.D., senior author of the study and Head of the Molecular and Developmental Biology Laboratory at Memorial Sloan-Kettering. "Our study shows that the loss of just one PTEN gene is enough to interrupt cell signaling and begin the process of uncontrolled cell growth."

Mutations of the PTEN gene are found in a large number of human tumors. These include cancers of the breast, prostate, endometrium, ovary, and colon, as well as melanoma, glioblastoma. and lymphoma. The inherited inactivation of one copy of the PTEN gene also results in three syndromes associated with an increased susceptibility to develop tumors.

In mice, the complete disruption of PTEN function leads to early embryonic death. Mice with a mutation in one PTEN copy (PTEN+/-) were found to have a high incidence of tumors. The most commonly occurring tumors were cancers of the colon, prostate, and thyroid. The scientists also found that the mouse immune system was unable to signal the white blood cells called lymphocytes to arrest their growth and die. Instead, the cells proliferated until they were fatal to the entire organism. In addition, most of the PTEN +/- mice developed a lupus-like autoimmune disease in which lymphocytes attack their own organs.

"Despite the commonly held belief that both pairs of the PTEN tumor suppressor gene must be mutated to inhibit apoptosis, our laboratory studies showed something different," explains Antonio Di Cristofano, Ph.D., of the Molecular and Developmental Biology Laboratory and first author of the study. "Loss of just one copy of PTEN is enough to initiate a progressive accumulation of lymphocytes which are unable to commit suicide after their job is done, and are thus prone to start attacking the organism itself. These cells can accumulate further damage in their genes, which then results in the development of malignant tumors. For all these reasons, the life expectancy of the PTEN+/- mice is cut in half," said Dr. Di Cristofano.

Dr. Pandolfi said the findings are likely to have clinical implications for persons with cancer and certain autoimmune disorders because tests for PTEN mutations already exist. It may be possible, he noted, to make specific recommendations for screening, early detection and treatment for these individuals based on whether mutations are detected in one copy of the PTEN gene. Further research is required in this area, however, before definitive clinical recommendations can be made. Dr. Pandolfi and his colleagues plan additional research to explore the relationship between autoimmune disorders and PTEN mutations in humans.

The study published in Science is the work of Drs. Pier Paolo Pandolfi, Antonio Di Cristofano, Parasevki Kotsi, and Carlos Cordon-Cardo, of Memorial Sloan-Kettering, and Drs. Keith B. Elkon and Yu Feng Peng, of the Hospital for Special Surgery, Weill Medical College of Cornell University.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Throughout its long distinguished history, the Center has played a leadership role in defining the standard of care for patients with cancer. In 1999, Memorial Sloan-Kettering was named the nation's best cancer care center for the seventh consecutive year by U.S. News & World Report.


Story Source:

The above story is based on materials provided by Memorial Sloan-Kettering Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

Memorial Sloan-Kettering Cancer Center. "Mutation In PTEN Gene Can Cause Cancer And Autoimmune Disease." ScienceDaily. ScienceDaily, 27 September 1999. <www.sciencedaily.com/releases/1999/09/990927065349.htm>.
Memorial Sloan-Kettering Cancer Center. (1999, September 27). Mutation In PTEN Gene Can Cause Cancer And Autoimmune Disease. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/1999/09/990927065349.htm
Memorial Sloan-Kettering Cancer Center. "Mutation In PTEN Gene Can Cause Cancer And Autoimmune Disease." ScienceDaily. www.sciencedaily.com/releases/1999/09/990927065349.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
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