Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New genetic marker characterizes aggressiveness of cancer cells

microRNA suppresses genes that trigger cancer progression

Levels of a small non-coding RNA molecule called let-7 appear to define different stages of cancer better than some of the "classical" markers for tumor progression, researchers from the University of Chicago report in the June 25, 2007, early online edition of the Proceedings of the National Academy of Sciences.

By suppressing genes that are active in the developing embryo, silenced just before birth, and re-activated years later in many advanced cancers, the let-7 family of "microRNAs"—tiny snippets of RNA that can put the brakes on expression of selected genes—appears to prevent human cancer cells from reasserting their prenatal capacity to divide rapidly, travel and spread.

Since they were first discovered in 1993, there had been growing interest in microRNAs and their role in gene regulation. Hundreds of these tiny molecules, about 20 nucleotides in length, have been discovered, scattered throughout the human genome. They act in most cases by attaching themselves to specific sites on messenger RNA, where they block ribosome access and thus prevent production of that protein.

... more about:
»HGMA2 »HMGA2 »MicroRNA »RNA »let-7 »ovarian »ovarian cancer

"There may be no human cancer that is not regulated by microRNAs," said study author Marcus Peter, professor in the Ben May Department for Cancer Research at the University of Chicago, "and among microRNAs, let-7 appears to be a key player in preventing a cancer from becoming more aggressive."

"We found that expression levels of let-7 can discriminate more effectively between more and less advanced stages of cancers than any other microRNA," Peter said. "We suspect that loss of members of the let-7 family may be a major determinant of cancer progression."

Understanding how microRNAs such as let-7 keep cancers in check could also point toward a whole new class of anti-cancer therapies, he suggested.

Peter and colleagues focused their initial studies on a standard panel, known as NCI60, of 60 human tumor cell lines that can genetically be divided into two large groups, which they called superclusters 1 and 2. Supercluster 1 cells may represent less differentiated, more aggressive stages of cancer. In contrast, supercluster 2 cells express a gene signature that is consistent with more differentiated, less aggressive cancers.

They tracked down one of let-7's primary targets, a gene called HMGA2, which is overexpressed in a wide variety of cancers. Tumor cells with high levels of let-7, the researchers found, had low levels of HGMA2 and tumor cells with low expression of let-7 expressed high amounts of HMGA2.

Next, they turned to a colleague, gynecologic oncologist Ernst Lengyel, an assistant professor of obstetrics and gynecology at the University of Chicago, whose research group focuses on ovarian cancer. Their theory was first confirmed with ovarian cancer cell lines and then the Peter/Lengyel team tested HGMA2 protein levels in tumor samples from 100 patients with ovarian cancer.

Neither normal ovarian tissue nor benign ovarian tumors expressed HGMA2, they found. However full blown carcinoma expresses large quantities of HMGA2. They also found that a high level of HGMA2 was highly correlated with poor prognosis, and that high HGMA2 levels were closely tied to low let-7 expression.

By combining the two measures, high HGMA2 and low let-7, they could separate the patients into two groups, and predict outcome. Five-year progression-free survival for patients with high let-7 and low HGMA2 was nearly 40 percent. For patients with low let-7 and high HGMA2, it fell to less than 10 percent.

"Our data suggests that human tumors can be divided into two major subtypes, the let-7hi and let-7lo-expressing tumor cells," the authors write. This separation may not be restricted to ovarian cancer, or to the NCI60 panel of tumor cells, they suggest, but could apply to a multitude of tumor types.

"There is growing evidence that large-scale gene-expression patterns can be regulated by microRNAs", Peter said. "Many of them are beginning to be expressed shortly before birth, where they turn off genes that were necessary for the rapidly developing embryo. Probably a number of embryonic genes, after being turned off for decades, are reexpressed in cancer cells, enabling those cells to regain their embryonic capacity to move around and invade other tissues."

The loss of let-7, the authors argue, could be seen as one crucial step in this process of tumor progression. One of its functions, they argue, is to maintain differentiated states by preventing the expression of embryonic genes such as HMGA2.

No rapid test of let-7 level is available for clinical use. "The levels are difficult to quantify in clinical samples", Peter said but "technology is exploding right now. We may be able to do this clinically before too long."

John Easton | EurekAlert!
Further information:

Further reports about: HGMA2 HMGA2 MicroRNA RNA let-7 ovarian ovarian cancer

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>