Featured Research

from universities, journals, and other organizations

Scientists Issue Telomerase Caution

Date:
June 16, 2000
Source:
Cold Spring Harbor Laboratory
Summary:
The enzyme telomerase has received a great deal of attention since 1998 when researchers showed that expressing this enzyme in human tissue culture cells significantly extended the life-span of the cells. Now, however, scientists report that using telomerase to extend the life-span of human tissue culture cells is associated with activation of the c-myc oncogene and thus may present some level of cancer risk if the cells are intended for therapeutic use in humans.

Cold Spring Harbor, NY -- The enzyme telomerase has received a great deal of attention since 1998 when researchers showed that expressing this enzyme in human tissue culture cells significantly extended the life-span of the cells. Telomerase expression was immediately recognized as a useful strategy for growing the large number of cells required for cell-based therapeutic procedures. Now, however, scientists report that using telomerase to extend the life-span of human tissue culture cells is associated with activation of the c-myc oncogene and thus may present some level of cancer risk if the cells are intended for therapeutic use in humans.

Related Articles


David Beach, of the Wolfson Institute for Biomedical Research (University College London) and his colleagues reported these findings in the June 15 issue of Nature. Joining Beach in the study were Jing Wang of Genetica, Inc. (Cambridge, Massachusetts) and Gregory Hannon of Cold Spring Harbor Laboratory.

The ends of chromosomes, called telomeres, consist of specialized repeated sequences of DNA (TTAGGG in humans) that serve to maintain the integrity of the chromosome. In the absence of telomerase, telomeres shorten with each cell division. Eventually, cells stop dividing when they sense that their telomeres are too short to maintain chromosomal integrity. In contrast, telomerase maintains telomere length by adding nucleotides one at a time to existing chromosomal ends in a regulated fashion.

Experiments in other laboratories had indicated that the use of telomerase expression to extend the life-span of cultured cells did not appear to transform these cells into a hyperproliferative, cancerous state. Now, Beach and his colleagues have shown that at least one hallmark of cancer cells is observed in such cells, namely, activation of the c-myc oncogene.

Frequently, cells grown in culture--such as the human mammary epithelial cells (HMEC) used in this study--undergo 50 to 60 population doublings before they stop growing or "senesce." To determine whether permanent telomerase expression was necessary to enable HMEC cells to continue growing beyond their usual senescence point, Beach and his colleagues employed a retrovirus that carried a gene encoding human telomerase. After 40 doublings, HMEC cells were infected with the retrovirus, and the resulting telomerase expression enabled the cells to divide beyond their usual senescence point. Then the scientists used a genetic trick to eliminate the retroviral copy of the telomerase gene, thus preventing any further telomerase gene expression. Or so they thought.

To their surprise, telomerase activity remained high in the cells for at least 20 population doublings after the retrovirus-borne telomerase gene was eliminated. This meant that expression of the cells' own telomerase genes had been unexpectedly switched on.

Beach, Wang, and Hannon (and their associates) had previously shown that the potent transcription factor encoded by the c-myc oncogene stimulates telomerase gene expression. Thus, they reasoned that the elevated telomerase expression they observed in the recent study might be a consequence of c-myc oncogene activation.

Consistent with this idea, the researchers observed that the expression level of c-myc was two- to three-fold higher in cells that had been immortalized (enabled to grow beyond their usual senescence point) by introduction of the retrovirus-borne telomerase gene. This degree of c-myc overexpression was similar to that in a breast cancer cell line the researchers included as a control. Although the immortalized HMEC cells were not fully transformed into a cancerous state, elevated c-myc expression is a major step in the multistep process leading to the malignant transformation of cells.

Altered expression of the c-myc oncogene is observed in approximately 70,000 fatal cancers per year in the United States. Therefore, the new study indicates that the use of telomerase expression to extend the life-span of cultured cells for therapeutic purposes must be approached with caution.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

Cold Spring Harbor Laboratory. "Scientists Issue Telomerase Caution." ScienceDaily. ScienceDaily, 16 June 2000. <www.sciencedaily.com/releases/2000/06/000615074751.htm>.
Cold Spring Harbor Laboratory. (2000, June 16). Scientists Issue Telomerase Caution. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2000/06/000615074751.htm
Cold Spring Harbor Laboratory. "Scientists Issue Telomerase Caution." ScienceDaily. www.sciencedaily.com/releases/2000/06/000615074751.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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