The role of StarD13 in breast cancer cell proliferation and motility. (c2012)

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dc.contributor.author Hanna, Samer J.
dc.date.accessioned 2013-03-04T09:25:53Z
dc.date.available 2013-03-04T09:25:53Z
dc.date.copyright 2012 en_US
dc.date.issued 2013-03-04
dc.date.submitted 2012-06-07
dc.identifier.uri http://hdl.handle.net/10725/1483
dc.description Includes bibliographical references (leaves 65-80). en_US
dc.description.abstract Breast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Cell migration, is a complex process, which requires the dynamic regulation of actin cytoskeleton. Members of the Rho subfamily of small GTPbinding proteins (GTPases) play a central role in breast cancer cell motility. The switch between active GTP-bound and inactive GDP-bound state is regulated by Guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and Guaninenucleotide dissociation inhibitors (GDIs). Here we study the role of StarD13, a newly identified Rho-GAP that specifically inhibits the function of RhoA and Cdc42. We aim to investigate its role in breast cancer proliferation and metastasis. The level of expression of this Rho-GAP in tumor tissues of different grades is assayed using immunohistochemistry. Moreover, the role of StarD13 in breast cancer cell lines is studied using two approaches. StarD13 is overexpressed using a StarD13-GFP construct, in the second approach StarD13 is knocked down using a specific siRNA. The effect on the activity of Rho-GTPases is observed using pull down activation assay, which confirmed StarD13 as a negative regulator for Rho and Cdc42 but not for Rac. Our results also showed that StarD13 plays a negative role in cellular proliferation. Moreover to investigate the role of StarD13 in cell motility, StarD13 knock down resulted in an inhibition of cell motility and cells were not able to detach their tail and move forward. Being a Rho-GAP and localizing to focal adhesions, we hypothesize that StarD13 is inhibiting Rho to allow the formation of Rac-dependent focal complexes and the detachment of focal adhesions for the cells to move forward. However, our results show that the knockdown of StarD13 seems to promote breast cancer cell invasion in vitro. en_US
dc.language.iso en en_US
dc.subject Breast -- Cancer -- Molecular aspects en_US
dc.subject Cells -- Motility en_US
dc.subject Cell proliferation en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title The role of StarD13 in breast cancer cell proliferation and motility. (c2012) en_US
dc.type Thesis en_US
dc.term.submitted Spring en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school Arts and Sciences en_US
dc.author.idnumber 200904037 en_US
dc.author.commembers Dr. Sandra Rizk-Jamati
dc.author.commembers Dr. Roy Khalaf
dc.author.woa OA en_US
dc.description.physdesc 1 bound copy: xviii, 80 leaves; ill. (some col.); 31 cm.; available at RNL. en_US
dc.author.division Biology en_US
dc.author.advisor Dr. Mirvat El-Sibai
dc.keywords StarD13 en_US
dc.keywords Breast Cancer en_US
dc.keywords Cell proliferation en_US
dc.keywords Cell motility en_US
dc.keywords Focal Adhesions en_US
dc.keywords Cell invasion en_US
dc.identifier.doi https://doi.org/10.26756/th.2012.36 en_US
dc.publisher.institution Lebanese American University en_US

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