Cancers 2012, 4(2), 475-489; doi:10.3390/cancers4020475
Article

P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

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Received: 27 February 2012; in revised form: 13 April 2012 / Accepted: 13 April 2012 / Published: 25 April 2012
(This article belongs to the Special Issue Tumor Stroma)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis.
Keywords: p190B RhoGAP; mitosis; chromosome segregation; centrosome; aneuploidy; Rho GTPases; breast cancer
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MDPI and ACS Style

Hwang, M.; Peddibhotla, S.; McHenry, P.; Chang, P.; Yochum, Z.; Park, K.U.; Sears, J.C.; Vargo-Gogola, T. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells. Cancers 2012, 4, 475-489.

AMA Style

Hwang M, Peddibhotla S, McHenry P, Chang P, Yochum Z, Park KU, Sears JC, Vargo-Gogola T. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells. Cancers. 2012; 4(2):475-489.

Chicago/Turabian Style

Hwang, Melissa; Peddibhotla, Sirisha; McHenry, Peter; Chang, Peggy; Yochum, Zachary; Park, Ko Un; Sears, James Cooper; Vargo-Gogola, Tracy. 2012. "P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells." Cancers 4, no. 2: 475-489.

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