Diagnostic Marker May Help Predict Response to Cervical Cancer Treatment

UCLA RESEARCH BRIEF

FINDINGS

UCLA researchers have identified a potential diagnostic marker that could help predict how likely someone with cervical cancer is to respond to the standard treatment of chemotherapy and radiation.

The scientists found that PACS-1, a gene that resides on a small segment of the long arm of chromosome 11, is overexpressed in cancer tissues, which can result in cancer growth and spread. Further, they discovered that translocation of the PACS-1 protein from outside to inside the cell nucleus -- a function required for normal cell growth -- plays a role in the development of cervical cancer that is resistant to chemotherapy and radiation. Higher levels of PACS-1 expression in the nucleus could indicate resistance to the treatment, the researchers say.

BACKGROUND

Cervical cancer is the second leading cause of cancer-related death among women worldwide. While infection with human papillomaviruses plays a significant role in cervical cancer development, the presence of a virus alone is not enough to cause cancer; genetics and environmental factors such as smoking and poor eating habits also play a role. Therefore, it is important to identify biological markers as targeting agents for diagnosis and treatment.

METHOD

The researchers performed a western blot, a technique for detecting specific protein molecules from among a mixture of proteins, on cervical tumors and healthy cervical tissue and discovered an overexpression of PACS-1 in the tumor tissues. The team then developed in vitro human cell line models to assess the protein's role in cell growth. Finally, they used a fluorescence-activated sorter analysis to help determine if the overexpression of PACS-1 protein was associated with cancer chemoresistance.

IMPACT

If confirmed in animal studies, the use of PACS-1 as a diagnostic marker could help lead to the development of therapeutic strategies to overcome treatment resistance in cervical cancer. Alternative methods of treatment, including the inhibition of PACS-1 expression, could be used in combination with chemotherapy or immune system-activating agents.

AUTHORS

The study's senior author is Eri Srivatsan, a professor of surgery at the David Geffen School of Medicine at UCLA and member of UCLA's Jonsson Comprehensive Cancer Center and Molecular Biology Institute. The first author is Mysore Veena, a scientist at the Geffen School of Medicine.

JOURNAL

The study is published online in the Journal of Biological Chemistry.

FUNDING

The research was supported in part by the National Cancer Institute and the Veterans Affairs Greater Los Angeles Healthcare System.

Reference: Veena MS, Raychaudhuri S, Basak SK, et al. Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer. J. Biol. Chem. 2020;295,17169-17186. doi:10.1074/jbc.RA120.014048

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