Studies supported by the VCU Wright Center connect mammary hormone to breast cancer progression

charles clevenger using microscope

The hormone prolactin has long been understood to play a vital role in breast growth and development and the production of milk during pregnancy. But a pair of recent studies conducted at Virginia Commonwealth University finds strong evidence that prolactin also acts as a major contributor to breast cancer development and that the hormone could inform the creation of targeted drugs to treat multiple forms of the disease.

Hormones have proteins on their cell surface called receptors that receive and send biological messages and regulate cell function. Through research published in npj Breast Cancer, VCU Massey Cancer Center researcher Charles Clevenger, M.D., Ph.D., and his lab discovered a new, altered form of the prolactin receptor called the human prolactin receptor intermediate isoform (hPRLrI) that directly drives breast cancer. The researchers observed that this modified version of the prolactin receptor interacted with other forms of the receptor to turn benign breast cells into malignant ones, and the presence of hPRLrI in breast cancer cells was associated with triple negative breast cancer, a rapid rate of cell reproduction and poor outcomes.

“This research challenges the dogma that prolactin only functions in milk production and highlights the unique discovery that the hormone can contribute to breast cancer,” said Clevenger, who is the associate director for precision oncology, Carolyn Wingate Hyde Endowed Chair in Cancer Research and member of the Cancer Biology research program at Massey as well as chair of the Department of Pathology at the VCU School of Medicine. “By understanding how the prolactin receptor correlates to breast cancer, novel therapeutic and prognostic agents can be developed to effectively treat the disease.”

Amy Olex, M.S., senior bioinformatics specialist at the VCU Wright Center for Clinical and Translational Research, supported the research through use of the data from the The Cancer Genome Atlas, a genomics program at the National Cancer Institute. She downloaded the data and performed the RNA sequencing analysis to quantify the hPRLrI isoform-specific expression. And she performed the differential expression analysis of hPRLrI-stratified patients in the atlas. Through her work, the research is partially funded by the National Center for Advancing Translational Sciences (UL1TR002649).

Clevenger said these findings support the argument that future approaches in drug design may need to specifically target hPRLrI, and could ultimately inform advanced diagnostic applications for breast cancer as well.

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