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Eberly College of Arts and Sciences


Microbiology, Immunology, and Cell Biology


Enhanced expression and activity of cSrc are associated with ovarian cancer progression. Generally, cSrc does not contain acti- vating mutations; rather, its activity is increased in response to signals that affect a conformational change that releases its auto- inhibition. In this report, we analyzed ovarian cancer tissues for the expression of a cSrc-activating protein, AFAP-110. AFAP-110 activates cSrc through a direct interaction that releases it from its autoinhibited conformation. Immunohistochemical analysis re- vealed a concomitant increase of AFAP-110 and cSrc in ovarian cancer tissues. An analysis of the AFAP-110 coding sequence revealed the presence of a nonsynonymous, single-nucleotide polymorphism that resulted in a change of Ser403 to Cys403. In cells that express enhanced levels of cSrc, AFAP-110403C directed the activation of cSrc and the formation of podosomes indepen- dently of input signals, in contrast to wild-type AFAP-110. We therefore propose that, under conditions of cSrc overexpression, the polymorphic variant of AFAP-110 promotes cSrc activation. Further, these data indicate a mechanism by which an inherited genetic variation could influence ovarian cancer progression and could be used to predict the response to targeted therapy.

Source Citation

Zhu, M., Fitzgerald, E. F., Gelberg, K. H., Lin, S., & Druschel, C. M. (2010). Maternal Low-Level Lead Exposure and Fetal Growth. Environmental Health Perspectives, 118(10), 1471–1475.


Copyright © 2010 Neoplasia Press, Inc. All rights reserved 1944-7124/10/$25.00DOI 10.1593/tlo.10106www.transonc.comTranslationalOncologyVolume 3 Number 4August 2010pp. 276–285276



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