The lesser-known lookalike of a key protein appears to play a critical role in the growth of cancer cells, according to City of Hope researchers. Their findings, published online Jan. 7 in Molecular Cancer Therapeutics, point to a potential new anticancer strategy.
|Yun Yen and his research team may have found a potential strategy for improving current chemotherapy by targeting proteins involved in DNA synthesis. (Photo by Kaminsky Productions)|
A team of researchers led by Yun Yen, M.D., Ph.D., Dr. & Mrs. Allen Y. Chao Chair in Developmental Cancer Therapeutics, found that a protein called p53R2 seems to suppress the growth of cancer cells.
The protein is a homologue — that is, it is nearly identical to — a part of another protein called ribonucleotide reductase, which produces the building blocks of DNA.
Yen, chair of the Department of Molecular Pharmacology, devotes much of his research to understanding the role ribonucleotide reductase plays in cancer development and metastasis and to searching for drugs that might interact with the enzyme to overcome cancer cells.
The similarity of p53R2 to the ribonucleotide reductase subunit sparked the researchers’ interest in the protein, Yen said.
Previous research showed that the expression of p53R2 is poorly regulated in human cancer cells as compared to normal cells; however, the protein’s role in cancer remained unclear. This led the City of Hope scientists to study cancer cells that do not produce any p53R2. They found the cells ramped up the activity of certain genes that speed cell growth, which could let cancer run wild.
They then checked cells that had high levels of p53R2 and found those cells had increased levels of genes that block cell growth, a condition that could rein in cancer cells.
The team next looked at the effect of p53R2 levels on cells exposed to the chemotherapy drug adriamycin, which damages DNA in rapidly growing cells such as tumor cells.
The researchers found that when they exposed cells with low p53R2 to adriamycin, the cells’ DNA suffered greater damage.
“The results suggest p53R2 participates in both cell proliferation and DNA damage repair signaling pathways, and drug discovery targeting p53R2 should take this under consideration,” said Keqiang Zhang, Ph.D., postdoctoral fellow in Yen’s lab and lead author on the study.
While the scientists note that more research is necessary to understand fully the role of p53R2 in cancer growth and development, they hope the work eventually will lead to studies of targeted drugs that might control cancer through p53R2.
Other researchers on the study include Jun Wu, Ph.D., Xiwei Wu, M.D., Ph.D., Xiaochen Wang, Ph.D., Yan Wang, Ning Zhou, Mei-ling Kuo, Ph.D., Xiyong Liu, Ph.D., Bingsen Zhou, Ph.D., Lufen Chang, Ph.D., and David Ann, Ph.D. The study was supported by a grant from the National Cancer Institute.