Next Article in Journal / Special Issue
T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
Previous Article in Journal
Radical Decisions in Cancer: Redox Control of Cell Growth and Death
Previous Article in Special Issue
The Dynamics of Developmental and Tumor Angiogenesis—A Comparison

P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617, USA
Department of Molecular and Human Genetics, Baylor College of Medicine, John P. McGovern Campus, NABS-0250, Houston, TX 77030, USA
Department of Biology, Southwestern Adventist University, 100 W. Hillcrest, Keene, TX 76059, USA
Author to whom correspondence should be addressed.
Cancers 2012, 4(2), 475-489;
Received: 27 February 2012 / Revised: 13 April 2012 / Accepted: 13 April 2012 / Published: 25 April 2012
(This article belongs to the Special Issue Tumor Stroma)
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. View Full-Text
Keywords: p190B RhoGAP; mitosis; chromosome segregation; centrosome; aneuploidy; Rho GTPases; breast cancer p190B RhoGAP; mitosis; chromosome segregation; centrosome; aneuploidy; Rho GTPases; breast cancer
Show Figures

Figure 1

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

Find Other Styles

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Back to TopTop