Navigation Links
UCSF scientists illuminate how microRNAs drive tumor progression
Date:9/17/2009

UCSF researchers have identified collections of tiny molecules known as microRNAs that affect distinct processes critical for the progression of cancer. The findings, they say, expand researchers' understanding of the important regulatory function of microRNAs in tumor biology and point to new directions for future study and potential treatments.

The researchers refer to these microRNA collections as signatures, and their study results are reported in the September 15 issue of "Genes & Development.'' The study, available online at http://genesdev.cshlp.org/, was led by the laboratory of Douglas Hanahan, PhD, an American Cancer Society Research Professor in the Department of Biochemistry and Biophysics at UCSF.

Approximately five percent of all known human genes encode, or produce, microRNAs, yet scientists are only now nearly a decade after their discovery -- beginning to unlock the mystery of their functions.

MicroRNAs are snippets of single-stranded RNAs that prevent a gene's code from being translated from messenger RNA into proteins, which are essential for cell growth and development. Produced in the nucleus and released into the cytoplasm, they home in on messenger RNAs that possess a stretch that is complementary to their genetic sequence. When they locate them, they latch on, preventing the messenger RNA from being processed by the protein-making machines known as ribosomes. As such, microRNAs are able to ratchet down a cell's production of a given protein.

Over the last several years, several groups have identified hundreds of microRNAs that are deregulated between normal tissue and tumors, however researchers only understand what a handful of these powerful regulators are doing to drive tumor formation.

"Virtually all cancers acquire approximately six distinct capabilities en route to tumor formation," said lead author Peter Olson, PhD, a postdoctoral fellow in the Diabetes Center and Helen Diller Family Comprehensive Cancer Center at UCSF. "When a cancer researcher observes a gene or microRNA go awry, it can be challenging to understand how that microRNA impacts tumorigenesis."

To home in on the question, the authors turned to a mouse model of pancreatic neuroendocrine tumors in which lesions go through discrete stages before culminating in invasive and metastatic carcinomas. In the three-year microRNA study, they found that cells in the mouse model developed and functioned normally but started to replicate uncontrollably at five weeks. Several weeks later, some pancreatic islets had become angiogenic (forming new blood vessels) a step in the journey from a dormant state to a malignant state -- though had not yet formed a tumor. By 10 weeks, a subset of angiogenic lesions had progressed to the tumor stage, and by week 16, a small percentage of mice had developed liver metastasis.

"This represents the spectrum of stages that we think are important for all tumors, including human disease," said Olson.

By measuring the expression level of all known microRNA in pre-tumor stages, tumors and metastases, the authors were able to associate deregulated microRNAs with processes such as hyperproliferation, angiogenesis and metastasis.

Focusing on the metastatic signature, researchers found -- in one of the most striking observations of the project -- that tumors bore a startlingly divergent microRNA expression pattern compared to primary tumors. Moreover, a subset of primary tumors showed more similarity to metastases than to other primary tumors.

"If you can identify tumors that have an increased propensity to metastasize, then it would have a very important clinical application," said Olson. "A lively debate in metastatic research has centered around whether primary tumor cells must suffer an additional mutation that endows that cell with a metastatic capability, or whether certain mutational combinations that are responsible for primary tumor formation also significantly increase the propensity of that cell to metastasize. These data provide evidence for the latter.''


'/>"/>

Contact: Elizabeth Fernandez
efernandez@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

Related medicine news :

1. Glaxo Official Memo Urged Scientists to Withhold Information About Paxils Risks, Trial Hears; Pharmaceutical Industry Today Offers Complete News Coverage
2. University of Hawaii at Manoa CRCH scientists report adulthood body size associated with cancer risk
3. Scientists Spot Key to Breast Cancer Spread
4. Scientists Find Clue to Dangerous Side Effect of MS Drug
5. Scientists Spot Clue to Cancers Aggressiveness
6. Scientists Turn Off Obesity Switch in Mice
7. NIBIB scientists increase imaging efficiency in cell structure studies
8. Scientists Make Sweet Monkey Music
9. Scientists from University of Hawaii at Manoa find genetic marker
10. Nottingham scientists commissioned for urgent swine flu research
11. Ellison Medical Foundation awards more than $1 million to mid-career scientists
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... ... , ... A first-time look at workers’ compensation claims in Kentucky found that ... Research Institute (WCRI) announced, and that costs per claim were stable between 2009 ... , found that indemnity costs per claim and benefit delivery expenses per claim were ...
(Date:4/28/2016)... Tamarac, FL (PRWEB) , ... April 28, 2016 , ... ... body recovery supplement GlycoLoad at this week’s 2016 Europa Games Get Fit and ... health conscious consumers alike, the Europa Orlando Expo coming up April 29-30, was selected ...
(Date:4/28/2016)... ... , ... Denise McCormick Baich had written poetry dating back to her childhood, but after several ... tsunami and took on a more spiritual tone. The desire to put the words on ... it than just file it away. Friends would ask her how she wrote such wonderful ...
(Date:4/28/2016)... ... April 28, 2016 , ... North Hollywood dentist , Dr. Hamid ... is essential when it comes to dental accidents or critical dental problems. These issues ... losing a tooth. Toothaches, knocked-out teeth, chipped teeth, and many other issues can lead ...
(Date:4/28/2016)... ... April 28, 2016 , ... The USDA recently released its updated ... latest nutritional science. While there is a lot of information available in the report, ... the April 2016 issue of Harvard Men's Health Watch . , These ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... , April 28, 2016 ... Review, H1 2016" is a report that provides ... helps strengthen R&D pipelines by identifying new targets ... Company Profiles discussed in this H1 ... Farmaceutiche Riunite Srl, AbbVie Inc., Abiogen Pharma S.p.A., ...
(Date:4/27/2016)... --   , Total Sales ... Sales  Clinical sales grow 16% year-over-year  , ... OTCQX: MKEAY) inventor of Cellvizio®, the multidisciplinary confocal laser ... quarter ended March 31, 2016 and provided an update ... strategy. First Quarter 2016 Revenue Results by ...
(Date:4/27/2016)... Tie-up with Government hospitals as ... to save newborns   Fortis La Femme, ... collaboration with Breast Milk Foundation (BMF), a non-profit organization within ... Bank, ,Amaara, in Delhi-NCR today. This non-profit centre recognizes that ... and should be available to babies deprived of mother,s milk.  ...
Breaking Medicine Technology: