Proteins Associated With Poor Prognosis in Hormone Receptor-positive Breast Cancer Identified
April 1, 2012
- Activation of protein translation linked to more aggressive node-positive disease.
- Markers identified are regulated by PI3K/mTOR signaling pathway.
CHICAGO — Researchers have identified specific proteins involved in translation that when overexpressed or activated are associated with a poorer prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets, according to results presented at the AACR Annual Meeting 2012, held here March 31 - April 4.
“Overexpression or activation of some proteins involved in translation is associated with more aggressive node-positive breast cancers,” said Funda Meric-Bernstam, M.D., professor of surgical oncology at the University of Texas MD Anderson Cancer Center and medical director at the Institute of Personalized Cancer Therapy in Houston, Texas. “The results suggest that translational aberrations play an important role in cancer progression.”
Through analysis of tumors from 190 patients with stage 1 to stage 3 hormone receptor-positive breast cancer, the researchers found that increased phosphorylation of ribosomal protein S6 and translation initiation factor 4E-binding protein 1, increased expression of eukaryotic elongation factor 2 kinase and decreased expression of programmed cell death protein 4 were associated with poor prognosis in hormone receptor-positive breast cancer.
“Gene expression involves translation of messenger RNAs into protein. The rate of translation is under critical control at many levels; however, recently, several abnormalities in translation have been described in cancer,” said Meric-Bernstam. “We used a functional proteomics approach to quantify the expression and phosphorylation of several factors associated with translation. Several of these proteins have been suggested to play a role in tumor aggressiveness.”
The markers identified are regulated by the PI3K/mTOR signaling pathway, a key oncogenic pathway activated in breast cancer and other cancers, according to Meric-Bernstam. Novel inhibitors of the pathway are being investigated in clinical trials.
“There are recent phase III clinical trial data suggesting that inhibiting mTOR signaling with everolimus, an mTOR inhibitor, in addition to endocrine therapy with aromatase inhibitors improves progression-free survival in hormone receptor-positive breast cancer,” Meric-Bernstam said. “Activation of the pathway conferring poor prognosis provides rationale as to why pathway inhibitors improve outcome.”
The study was funded by an AACR–Stand Up To Cancer Dream Team Award, Susan G. Komen for the Cure, the Society of Surgical Oncology Clinical Investigator Award and the National Institutes of Health Cancer Center Grant.
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