Ying Huang, MD, PhD (photo by Richard Whelsky)

Finding clues to the cause of lung adenocarcinoma

This is one of a series of articles focusing on lung cancer.

BY AMBER SMITH

Scientists have long searched for the cause of lung cancer, particularly lung adenocarcinoma, the type that commonly occurs in nonsmokers. Ying Huang, MD, PhD, believes a gene she’s been studying for more than two decades may provide some answers.

Huang, a professor in the department of pharmacology at Upstate, works in collaboration with M. Saeed Sheikh, MD, PhD, also a professor in the department of pharmacology. They have independently identified a gene called monoglyceride lipase, abbreviated to MGL, which may be important in how lung adenocarcinoma develops.

Comparing tissue samples from more than 340 patients, they found normal levels of MGL in healthy lung tissue but significantly reduced levels in a big portion of the cancerous lung tissue. In the case of lung cancer, the research team found more than 65% of lung cancer showed reduced MGL levels.

Huang suspected MGL to be a tumor suppressor, a gene whose presence prevents cancer from growing, but whose absence allows it to grow. To determine whether MGL is a tumor suppressor, the researchers introduced a copy of the MGL gene into lung and colon cancer cells and found that MGL suppressed cancer cell growth.

Then, to further assess MGL’s role in cancer development in animals, they deleted the MGL gene from laboratory mice. Initially they found no tumors developing in the animals up to 6 months of age. But when the mice reached 10 months, lung cancers — specifically lung adenocarcinomas — became apparent in a significant portion of the animals.

“These results indicate that this gene is important in preventing lung cancer,” Huang says.

She described the research in the journal Cell Death and Disease.

“Our studies, using animals as a model, demonstrate for the first time that MGL deficiency is an important contributing factor in the development of lung adenocarcinomas,” she wrote.

The mice also developed cancer in the spleen, liver and lymphoid tissues, but “lung neoplasms were the most common,” said Huang. Pathologists Christopher Curtiss, MD, Steve Landas, MD, and Rong Rong, MD, PhD, collaborated on these studies

by evaluating animal tissues. Doctoral students Renyan Liu and Xin Wang also participated in the project. Liu is now a research fellow at the Harvard School of Dental Medicine. Wang continues her thesis research in Huang’s lab.

Huang hopes that her work contributes to the understanding of how lung cancer develops. She wants to explore MGL’s potential as a lung cancer treatment, too. Her MGL studies have been funded by grants from the National Institutes of Health and the Michael E. Connolly Endowment for Lung Cancer Research. Her lab is seeking additional funding for further research.

To donate to the Michael E. Connolly Endowment for Lung Cancer Research at Upstate, contact the Upstate Foundation at 315-464-4416.

The role of genes in cancer

Oncogenes

Proto-oncogenes are genes that normally help cells grow. When a proto-oncogene mutates, or changes, or there are too many copies of it, it becomes a “bad” gene that can become permanently turned on or activated when it is not supposed to be. When this happens, the cell grows out of control, which can lead to cancer. That bad gene is called an oncogene.

Think of a cell as a car. For it to work properly, there need to be ways to control how fast it goes. A proto-oncogene normally functions like a gas pedal. It helps the cell grow and divide. An oncogene could be compared with a gas pedal that is stuck down, causing the cell to divide out of control.

Tumor suppressor genes

Tumor suppressor genes are normal genes that slow cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer.

A tumor suppressor gene is like the brake pedal on a car. It normally keeps the cell from dividing too quickly, just as a brake keeps a car from going too fast. When something goes wrong with the gene, such as a mutation, cell division can get out of control.

An important difference between oncogenes and tumor suppressor genes is that oncogenes result from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off).

Source: American Cancer Society

This article appears in the fall 2019 issue of Cancer Care magazine.