Breast cancer is the second leading cause of cancer-related mortality in women, with a 1 in 8 lifetime of risk for women in the United States. A key hurdle in developing better treatments for breast cancers is a lack of understanding at the molecular level of what promotes the growth of breast cancer cells, and why some breast cancers grow in response to estrogens, while others do not. In this regard, we are studying a relatively new and uncharacterized class of molecules called long non-coding RNAs (lncRNAs). In work during the previous round of funding of this grant, we discovered a lncRNA expressed in estrogen-responsive “luminal” breast cancers, which codes for a short polypeptide c...

Read More

Breast cancer is the second leading cause of cancer-related mortality in women, with a 1 in 8 lifetime of risk for women in the United States. A key hurdle in developing better treatments for breast cancers is a lack of understanding at the molecular level of what promotes the growth of breast cancer cells, and why some breast cancers grow in response to estrogens, while others do not. In this regard, we are studying a relatively new and uncharacterized class of molecules called long non-coding RNAs (lncRNAs). In work during the previous round of funding of this grant, we discovered a lncRNA expressed in estrogen-responsive “luminal” breast cancers, which codes for a short polypeptide called TSP1 (tumor-specific polypeptide 1). Our data indicate that TSP1 functions in the genome of cells to control gene expression and, ultimately, breast cancer biology. In the current application, we propose to study the molecular mechanisms by which TSP1 drives the proliferation, tumor formation, migration, invasion, and metastasis in breast cancers. We think that the molecular and biochemical features of TSP1 determines its ability to turn growth-regulating genes on or off, which in turn controls the growth and clinical phenotypes of breast cancers. Our experiments will test this hypothesis using an integrated set of state-of-the experimental approaches. Our studies will elucidate the molecular functions of TSP1 in breast cancers, as well as provide the research community with new tools and approaches for studying lncRNAs. Collectively, our studies will: (1) advance the way that breast cancer research is conducted, (2) provide a new marker with great diagnostic and prognostic potential, and (3) provide a new set of targets for controlling breast cancer cell growth, which have therapeutic potential. As such, the proposed studies have the potential to reduce the mortality of breast cancer.

Read Less