Joseph J. DiBartolomeo, Ph.D
(215) 707-4598
E-mail: [email protected]
Temple University School of Medicine
EMBARGOED UNTIL: Sunday March 29, 1998, 8:00 a.m. Eastern Time
NEW PATHWAY OFFERS HOPE FOR ANTI-CANCER AGENTS
A new pathway for tumor growth was reported today at the American Association for Cancer Research Meeting in New Orleans. "The Src-STAT-3 pathway plays a critical role in the growth of human tumors," indicates E. Premkumar Reddy, Ph.D., Director of the Fels Institute for Cancer Research at Temple University School of Medicine. According to Dr. Reddy, "This finding will offer the research community a target for the development of new categories of diagnostic tests and anti-cancer agents."
Today's announcement indicates that two separate pathways are now associated with the growth of human tumors. In recent years, proteins such as JAK kinases were believed to play a role in the activation of STATs, which are involved in the proliferation of both normal and cancer cells. However, this study examined the role of other proteins called Src kinases in the growth of human breast, prostate, ovarian and lung cancers.
Previous findings indicated the presence of activated STAT-3 in the nucleus of a vast majority of human breast, prostate, ovarian and lung cancer cell lines. Stat-3 activation is mediated via phosphorylation, which was previously thought to be associated with JAK kinases. This research shows that none of the JAK kinases were found to be in a phosphorylated state suggesting another pathway for activation of STAT-3.
To investigate a mechanism of STAT-3 phosphorylation, this study used an IL3-dependent cell line (32Dcl3) from normal mouse bone marrow. Findings indicate that the activation of Src kinases resulted in binding to and subsequent phosphorylation of STAT-3. According to Dr. Reddy, "Our results support the presence of Src kinases which activate STAT-3 resulting in its movement into the nucleus of a vast majority of these tumor cells."
Normal human cells do not typically exhibit this activated state of Src kinases and STAT-3, which remains in the cytoplasm. Findings also showed the ability to block the activation of STAT-3, using a mutant form of Src kinase, which inhibited cell proliferation and growth of human breast cancer cells. "The Src-STAT-3 pathway is activated in tumor cells and plays a critical role in the growth of human breast, prostate, ovarian and lung cancer," said Dr. Reddy.
Cancer is a devastating disease. Based upon statistics from the American Cancer Society, this year an estimated 564,800 Americans will die from cancer. It is the second leading cause of death exceeded only by heart disease. One of every four deaths in this country is from cancer. In addition, it is estimated that more than 1.2 million new cancer cases will be diagnosed in the U.S. this year.
"The importance of this discovery goes well beyond the identification of a new pathway," indicates Dr. Reddy. For example, the Src-STAT-3 pathway is also highly active in hormone-independent prostate tumor cells, which are highly metastatic. The appearance of phosphorylated STAT-3 in the nucleus of these cells is an indicator of a more metastatic form of cancer.
This research will appear in the April 2, 1998 issue of the international cancer journal "Oncogene."
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