Renewal of NIAMS grant allows team of scientists to build upon investigation into genetic control of metastatic cancer and osteoporosis

September 17, 2007

WORCESTER, Mass.—Recognizing the innovative research efforts put forth by a team of University of Massachusetts Medical School scientists investigating the genetic control of the metastasis of breast and prostate cancer, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has renewed a $9 million program project grant to research the restructuring of genes and the changes that occur in tumors that allow cancers to metastasize in bone.  Led by Principal Investigator Gary Stein, PhD, professor and chair of cell biology and deputy director of the UMass Memorial Cancer Center, the program, Bone Cell Structure and Gene Expression was originally funded in 1992 by a five-year NIAMS grant and has generated intriguing information into the molecular changes that take place during cancer metastasis. Stein and a multidisciplinary team of researchers will examine the organization, assembly and arrangement of genes, proteins and factors that control genes in bone formation and remodeling, focusing on two tumors of clinical relevance, breast and prostate cancer.

“Often, prostate cancer is detected as bone pain. The tumor has already made its way to bone, and if breast cancer is not detected early, it will also metastasize to bone,” said Stein, who is also the Gerald L. Haidak, MD, and Zelda S. Haidak Professor of Cell Biology. “These tumors cause tremendous discomfort and fractures. By identifying the changes in gene expression that lead to tumors metastasizing to bone, we can target a specific mechanism for therapy to potentially treat those tumors as well as osteoporosis.”

Faculty members, fellows and graduate students from the Department of Cell Biology, Department of Cancer Biology and other basic science and clinical groups within the institution will contribute to the project. The multidisciplinary team of basic scientists will study the network of regulatory proteins needed to support genes that are not only necessary for bone development, but also bone replacement, which occurs throughout a person’s life. They will also examine changes within the organization of proteins and genes in microenvironments of the cell’s nucleus and how those changes are associated with a tumor’s ability to metastasize to bone.

Stein, a widely respected expert in cell biology, has contributed considerably to the body of knowledge regarding the genetic mechanisms of cancer. This project interfaces with his Nuclear Structure and Gene Expression program project, which was renewed by the National Cancer Institute last year. Nuclear Structure and Gene Expression centers on the organization of genes, proteins and factors that control genes in a cancer cell, and a multidisciplinary team of researchers will study the dramatic reorganization of genes and regulatory proteins as it occurs through the onset and progression of cancer, specifically acute myelogenous leukemia and breast cancer.

“Initially, Nuclear Structure and Gene Expression was a project that explored gene regulatory mechanisms that are modified in tumor cells, and what emerged was the realization that it was in fact very clinically relevant,” Stein said. “It’s now a project that has really made the transition from an exploration of biological control in cancer cells to directly investigating control of early stages of cancer and the subsequent progression of cancer.”

Each gene and regulatory protein is located in a microenvironment within a cell nucleus, and when a gene or protein is not in its correct location, it compromises a cell’s function, Stein said. There is a requirement to be in the right place at the right time, and location is exceedingly important. Investigators will examine the architectural structure of genes and regulatory proteins, nuclear microenvironments and the mechanisms used to locate the genes and proteins within microenvironments. They will also explore how regulatory information is delivered to progeny cells during cell division and how to interfere with the process when genes or proteins are not delivered adequately during the early and late stages of cancer. The team of investigators will apply their insight into reorganization of genes in microenvironments of breast cancer cell nuclei towards developing novel approaches to selectively block the ability of breast cancer cells to move to and grow in bone.

“These program projects require a collaborative approach to complex problems. The University of Massachusetts Medical School provides a rich environment of communication among colleagues with diverse skill sets, and the success of our collaborations over the past 15 years is reflected by the fact that these program grants have been renewed multiple times,” said Stein. “These projects could not have progressed if it wasn’t for the Medical School and UMass Memorial Health Care’s commitment to collaboration.”

In addition to Dr. Stein, the principal investigator for the grant, other faculty members closely involved include: co-principal investigator Jane B. Lian, PhD, professor of cell biology; and senior investigators Janet L. Stein, PhD, professor of cell biology; André J. van Wijnen, PhD, associate professor of cell biology; Anthony N. Imbalzano, PhD, associate professor of cell biology; Jeffrey A. Nickerson, PhD, associate professor of cell biology; Lucia R. Languino, PhD, professor of cancer biology, cell biology and radiation oncology; Stephen N. Jones, PhD, associate professor of cell biology and cancer biology; and Martin Montecino, PhD, a professor at the University of Concepcion in Chile.


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Contact: Nicole Soucy, 508-856-2000