SIU School of Medicine

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Breast cancer and estrogen
Dr. Mo targets microRNAs

Dr. Mo

Estrogen plays a critical role in breast cancer development. About 70 percent of breast tumors have estrogen receptor (ER), which stimulates cancer cell growth. Targeting the estrogen-signaling pathway may provide first line breast cancer treatment. For example, several clinical drugs such as tamoxifen target ER. However, more than 30 percent of the ER-positive tumors fail to respond to tamoxifen therapy; other tumors frequently develop a resistance to tamoxifen. Although this is likely due to the activation of estrogen-independent signaling, the precise molecular mechanism is not fully understood. This is a significant challenge for physicians when determining the treatment options for ER-positive breast tumors. There are no reliable biomarkers for this subpopulation.

Evidence indicates that microRNAs could play an important role in breast cancer development and progression. MicroRNAs do not produce proteins but can regulate numerous protein-making genes and play a role in the estrogen-independent growth of tumors.

Yin-Yuan Mo, Ph.D., associate professor of medical microbiology and immunology, hypothesizes that microRNAs play a key role in regulation of the genes required for estrogen-independent proliferation. Deregulation of these microRNAs may cause resistance to tamoxifen.

Dr. Mo’s preliminary studies have identified that six microRNAs are sufficient to confer estrogen-independent growth and tamoxifen resistance. His team will be studying microRNAs of clinical specimens taken from breast cancer patients who were initially identified to be ER positive but failed to respond to tamoxifen.

Work continues to define the minimal number of microRNAs that can confer estrogen-independent growth. Although several microRNAs have been reported to play a role in tamoxifen resistance by targeting ER, the six microRNAs identified in this study have no effect on ER, suggesting that a novel mechanism is involved.

Better understanding these micro-RNAs will lead to identification of biomarkers that can help explain why tamoxifen can destroy some ER-positive tumors and not others. This will help physicians determine the best treatment for their breast cancer patients.