Nobel Laureate UM Researcher Identifies a Protein Receptor that Powerfully Stimulates Growth
New research from the University of Miami Sylvester Comprehensive Cancer Center shows that a protein receptor activated by a growth hormone plays a key role in the growth of a variety of cancers. This could have a major impact on cancers that are fueled by hormones, like most breast and prostate cancers. Nobel laureate Andrew V. Schally, Ph.D., M.D., M.S., a professor in the Department of Pathology and the Division of Hematology-Oncology at the University of Miami Leonard M. Miller School of Medicine, has long been a leader in the study of hormone-related cancers. He and his colleagues showed that a splice variant (SV1) of a hormone receptor stimulated breast cancer cells in the laboratory. The research is published in the March 12 edition of the Proceedings of the National Academy of Sciences.
SV1 is a hormone growth factor receptor – a protein molecule which “receives” and responds to growth hormone-releasing hormone (GHRH). Previous research showed that both the growth hormone-releasing hormone and the variant receptor of protein, SV1, played some role in a variety of malignancies, including prostate, pancreatic, kidney, breast, ovarian, and bone cancer. In a normal setting, GHRH binds to receptors in the pituitary gland and stimulates the release of growth hormone, which induces growth in normal tissues. How GHRH attached to and stimulated cancer cells wasn’t clearly understood.
In this study the researchers used a breast cancer cell line that did not have either the full-length receptor for GHRH (GHRHR) or the splice variant of the hormone receptor SV1. When they exposed those cells to GHRH they did not respond, which was expected. In subsequent tests, they forced the expression of both the full receptor and the SV1 in a line of breast cancer cells. In both cases, the sensitivity to GHRH was restored and the malignant cells were activated to divide and grow – in these experiments, at about double the rate of the control cells.
But the most important finding was that cells with the SV1, the splice variant, began to grow even without the added ligand growth hormone-releasing hormone, GHRH. In fact, in the absence of GHRH, the SV1 cells were five times more likely to stimulate tumor cell growth than the control cells – cells without either receptor. The cells with the full GHRHR receptor showed very little activity without the addition of the growth hormone. SV1 clearly plays an independent role in the stimulation of cancer growth.
“This paper demonstrates the physiological or pathological importance of GHRH,” said Schally, who also holds an appointment at the Miami Veterans Affairs Medical Center. “You must do this before you can proceed to working on therapies for these cancers because you have to show that it’s important and also try to elucidate the mechanism so you can attack it.”
GHRH, the growth hormone-releasing hormone, besides its role in controlling the release of growth hormone from the pituitary, may stimulate not only the initial cell to which it attaches but also surrounding tumor cells. Understanding how it, and the protein splice variant receptor, work may create new opportunities to block their roles in hormone-responsive cancer. Dr. Schally is a world leader in targeting hormone-related cancers and is largely responsible for the field of hormone ablation for the treatment of prostate and other cancers.
Schally came to the UM Miller School of Medicine and the Miami VA in September of 2005 from Tulane University and the New Orleans VA. “Our work was the first to identify this new growth factor which is present in a variety of cancers,” Schally said. “We’re the only ones who discovered this receptor of GHRH.” He worked with colleagues from the University of Athens Medical School in Greece and, in fact, one of the Greek co-authors, Nektarios Barabutis, Ph.D., is now with Dr. Schally in Miami continuing the work.
“Here in Miami we want to produce new, more powerful antagonistic analogs of GHRH so we’re more able to battle these hormone-dependent cancers,” said Schally, who has developed a number of hormone analogs, which can be powerful therapies against cancer. “So this paper is in line with that work.” The work is considered important enough that Dr. Schally has been invited by the journal Nature Clinical Practice to write a review on the clinical implications of GHRH, to be published this fall.
The study will be available March 12 at http://www.pnas.org/.
UM/Sylvester opened in 1992 to provide comprehensive cancer services and today serves as the hub for cancer-related research, diagnosis, and treatment at the University of Miami Leonard M. Miller School of Medicine. UM/Sylvester handles nearly 1,600 inpatient admissions annually, performs 3,000 surgical procedures, and treats 3,000 new cancer patients. All UM/Sylvester physicians are on the faculty of the Miller School of Medicine, South Florida’s only academic medical center. In addition, UM/Sylvester physicians and scientists are engaged in more than 250 clinical trials and receive more than $30 million annually in research grants. UM/Sylvester at Deerfield Beach opened in 2003 to better meet the needs of residents of Broward and Palm Beach counties. This 10,000 square-foot facility at I-95 and S.W. 10th Street offers appointments with physicians from six cancer specialties, complementary therapies from the Courtelis Center, and education and outreach events.