Associate Professor, Department of BiochemistryTumor Cell Biology ProgramPhD, Molecular Biology, 2000, University of Buenos Aires, ArgentinaPostdoc, 2000-08, University of Mississippi Medical Center, Jackson, MS
Contact information2500 N State St., Room G206Jackson, MS 39216Phone: (601) 984-1523E-mail: email@example.com
Breast cancer is the most common cancer and the second leading cause of cancer related deaths in females. G-protein coupled receptors (GPCRs) have widespread fundamental roles in cellular signaling. Heterotrimeric G-proteins are the molecular switches that turn on intracellular signaling cascades in response to the activation of GPCRs by extracellular stimuli. Therefore, G proteins have a crucial role in defining the specificity and temporal characteristics of the cellular response. G-proteins are switched on by GTP binding, and intrinsic GTPase activity hydrolyzes G-protein bound GTP to GDP to return to the basal state. However, G-proteins GTPase activity is too low to account for the rapid changes in G-protein activation/deactivation status observed in vivo. Regulator of G-protein signaling (RGS) proteins increase G-proteins GTPase activity thousands of times. The RGS protein family is ubiquitously expressed and RGS proteins are involved in any intracellular signaling process in which GPCRs are involved.
Although a highly attractive target, the role of RGS proteins in cancer is poorly understood. Screening for RGS proteins differentially expressed in MCF-7 breast cancer cells, which were grown in three dimensional extracellular matrixes that closely resemble the in vivo tumor microenvironment, we found that RGS22, the newest member of the RGS protein family, was significantly upregulated. Our studies have shown that RGS22 downregulation significantly decreases breast cancer cell proliferation, while RGS22 overexpression has the opposite effect. The recent development of specific RGS protein inhibitors makes RGS22 an exciting novel target to abolish or mitigate the exacerbated cell proliferation observed in breast cancers.
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