Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers uncover cellular clues to vitamin A resistance in lung cancer


Vitamin A deficiency has been associated with the development of lung cancer in laboratory studies. However, clinical trials of natural and synthetic derivatives of vitamin A, called retinoids, for the prevention of lung cancer have been largely unsuccessful in the general population. A new study in the November 16 issue of the Journal of the National Cancer Institute finds that targeting a previously unknown variant of a common retinoid receptor may restore the beneficial effects of retinoids in lung cancer cells.

Retinoids help regulate certain cellular functions in the body, such as cell growth and differentiation. These effects are mediated by retinoic acid receptors (RARs), including RAR-beta. Clinical trials have supported a role for the use of retinoids in the prevention of aerodigestive tract cancers. However, large randomized trials of retinoids and retinoic acid have shown that they are ineffective--and may even be harmful--in preventing lung cancer in smokers. Laboratory studies have found that, as lung cancer develops, RAR-beta becomes silenced, which makes cells resistant to retinoids. This loss of expression of RAR-beta is often seen in the lung cells of smokers.

W. Jeffrey Petty, M.D., previously of Dartmouth Medical School and now a faculty member of the Wake Forest University School of Medicine in Winston-Salem, N.C., and colleagues at Dartmouth set out to discover the mechanisms responsible for RAR-beta silencing and to see if they could restore the expression of RAR-beta using a compound called azacytidine. In the process of studying human bronchial epithelial cells that were resistant to treatment with retinoic acid, they discovered a previously unknown variant of one of the subtypes of RAR-beta.

The variant, called RAR-beta-1’, was expressed in normal lung cells and in cells sensitive to retinoic acid, but not in cells that were resistant to retinoic acid treatment or in lung cancer cells. When they treated cancer cells with azacytidine, RAR-beta-2 expression--but not RAR-beta-1’ expression--was restored, suggesting that the variant has characteristics and functions that are distinctly different from other known forms of RAR-beta and that it may play a role in retinoid resistance.

"Taken together, the data presented here directly implicate a critical role for RAR-beta-1’ in mediating retinoid biologic effects in the lung and perhaps other organ sites," the authors write. "The frequent repression of RAR-beta-1’ in lung carcinogenesis underscores its likely important biologic or clinical role. … Identification of pharmacologic approaches that restore RAR-beta-1’ expression would provide a basis for future retinoid-based combination strategies for lung cancer therapy or chemoprevention."

"The various isoforms of RAR-beta have complex relationships and interactions that appear to influence lung carcinogenesis, as illustrated by studies in mice and humans," Anita L. Sabichi, M.D., from the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues write in an accompanying editorial. "The differential expression and effects of different RAR-beta isoforms are a potential area for molecular-targeted lung cancer chemoprevention, and targeting RAR-beta-1’ to overcome retinoid resistance would be one potentially promising new approach."

Kate Travis | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

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

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>