IGF-1 is a polypeptide hormone that can influence growth, differentiation and survival of cells expressing the type 1 receptor (IGF-1R). Past clinical, epidemiological and experimental studies have strongly implicated IGF-1 as a contributing factor in the natural history of prostate cancer. However, very little has been done to prove absolutely that the expression or activation of the IGF-1 signaling pathway at physiologically relevant levels is sufficient to cause a healthy prostate cell to become a cancer cell.
Norman Greenberg, Ph.D., and colleagues conducted a pair of experiments by manipulating gene expression directly in the epithelial compartment of the mouse prostate gland to better understand the role of IGF-1R. In contrast to studies that correlated elevated levels of IGF-1 with the risk of developing prostate cancer, Greenberg’s research showed that eliminating IGF-1R expression in an otherwise normal mouse prostate caused the cells to proliferate and become hyperplastic. Although persistent loss of IGF-1R expression ultimately induced cell stasis and death, both of these processes are regulated by the tumor suppressor gene p53 that is commonly mutated in human prostate cancers. Hence the researchers hypothesized that tumors with compromised p53 might not respond predictably to therapies targeting IGF1 signaling.
To test their reasoning they conducted a second experiment by crossing mice carrying the prostate-specific IGF-1R knockout alleles with transgenic mice that develop spontaneous prostate cancer when p53 and select other genes are compromised. The results were as predicted: Prostate epithelial-specific deletion of IGF-1R facilitated the emergence of aggressive prostate cancer in the genetically-engineered tumor prone mice.
Published in the May 1 edition of Cancer Research, the study supports a critical role for IGF-1R signaling in prostate tumor development and identifies an important IGF-1R-dependent growth control mechanism, according to the authors. Title of the paper is “Conditional deletion of insulin-like growth factor-1 receptor in prostate epithelium.”
“If our predictions hold true, tumor cells with intact p53 may show the best response to therapy targeting the IGF-1R signal, however when p53 is not functioning normally, response to this therapy may not be as expected,” said Greenberg, the study’s corresponding author and a member of the Hutchinson Center’s Clinical Research Division.
Greenberg’s message to clinicians who administer IGF-R1 therapy: “We’re all hoping for good results but let’s proceed with caution.”
A search of the database for clinical trials registered with the National Cancer Institute found 18 trials in process that use therapies to inhibit IGF-R1. None of them include a tumor’s p53 status as a criterion for recruiting research participants, said Greenberg.
Dean Forbes | EurekAlert!
Hepatitis: liver failure attributable to compromised blood supply
19.12.2018 | Technische Universität München
Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering
Different eras of civilization are defined by the discovery of new materials, as new materials drive new capabilities. And yet, identifying the best material...
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
19.12.2018 | Materials Sciences
19.12.2018 | Materials Sciences
19.12.2018 | Life Sciences