Retinoblastoma dysfunction promotes pancreatic cancer cell growth

Indiana University cancer researchers have discovered that a protein that normally suppresses tumors actually promotes the growth and spread of pancreatic cancer.

Murray Korc, M.D., the Myles Brand Professor of Cancer Research at the Indiana University School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, and colleagues have shown that the retinoblastoma protein, a tumor suppressor, often malfunctions in . That dysfunction enables an inhibitory protein to promote pancreatic cancer growth.

The research was published online today in the Journal of Clinical Investigation.

As a result of the dysfunctional retinoblastoma protein, pancreatic cancer cells lose their ability to be inhibited by transforming growth factor-beta, or TGF-β, which is a key negative regulator of cell proliferation, according to Dr. Korc. Instead, the cells become stimulated by TGF-β due to activation of abnormal downstream signals known as non-canonical pathways.

The researchers also showed that TGF-β induces the expression of a growth-stimulating molecule called Wnt7b, which is not usually found in a normal adult pancreas. This combination allows TGF-β to directly enhance pancreatic cancer and survival.

Dr. Korc explained the combination of TGF-β and Wnt7b actions: "You have a cancer in which the accelerator is stuck to the floor and the brake is broken. But because of the malfunctioning retinoblastoma , the combined actions of TGF-β and Wnt7b convert the broken brake into a second accelerator."

Because the abnormal pathways activated by TGF-β and Wnt7b can be disrupted with drugs, Dr. Korc suggested that the findings open up a new avenue for exploring novel therapeutic combinations in pancreatic cancer.

However, Dr. Korc cautioned that more work remains to be done to determine how to best restore the regulatory functions of the and prevent the harmful actions of TGF-β.

"We have to figure out how to target these important pathways and to prevent bypass pathways from being activated," he said.

Related Stories

Feedback loop maintains basal cell population

Nov 01, 2012

Notch – the protein that can help determine cell fate – maintains a stable population of basal cells in the prostate through a positive feedback loop system with another key protein – TGF beta (transforming growth factor ...

Roles of T cells in disease cures and causes

Dec 06, 2013

T cells aren't as simple as you might think. Some attack infections and keep us healthy. Others allow tumors to grow. Understanding how these cells – the soldiers of our immune systems – develop and function ...

Recommended for you

Suppressing a protein reduces cancer spread in mice

2 hours ago

Scientists have found that decreasing the levels of or blocking a specific protein commonly found in humans and many other animals allowed them to slow the spread of two different kinds of cancer to the lungs ...

Bone loss drugs may help prevent endometrial cancer

13 hours ago

A new analysis suggests that women who use bisphosphonates—medications commonly used to treat osteoporosis and other bone conditions—have about half the risk of developing endometrial cancer as women who do not use the ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.