Cox-2 is a target gene of Rho GDP dissociation inhibitor beta in breast cancer cells

Schunke, Dario; Span, Paul N.; Ronneburg, Henrike; Dittmer, Angela; Vetter, Marcus; Kantelhardt, EJ; Mueller, Volkmar; Sweep, Fred C.G.J.; Thomssen, Christoph; Dittmer, J

doi:10.1016/s1359-6349(08)70433-6

Cited by 12 publications

(22 citation statements)

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“…Likewise, overexpression of D4-GDI in colorectal cancer cells promoted cell proliferation and in vitro motility and invasion [20]. On the other hand, our results show that the majority (78%) of malignant breast cancer and all metastatic lymph nodes samples had little or undetectable D4-GDI immunoreactivity which is in agreement with reports by others [12,25,33]. Within the malignant samples, those that were grade 2 (moderately differentiated, data provided by US Biomax) tumors had the lowest D4-GDI expression (Fig.…”

Section: Discussionsupporting

confidence: 92%

Association of D4-GDI expression with breast cancer progression

Rosado

Rodriguez‐Canales

Zhang

2012

CBM

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Abstract. D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis.

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Section: Discussionsupporting

confidence: 92%

Association of D4-GDI expression with breast cancer progression

Rosado

Rodriguez‐Canales

Zhang

2012

CBM

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“…Primers used for the amplification of the Rho-GDI· specific cDNA were as follows, forward primer: 5'-AACCGA GAGATAGTGTCCGGC-3', reverse primer: 5'-TCTTGA CGCCTTTCCTGTACG-3' (MWG Biotech). Primers for the detection of Rho-GDIß are described in Schunke et al (9). The cut-off for separating tumors with high Rho-GDI· levels from those with low levels was set at the median level of all 263 measured tumors from the tumor bank in the Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre (The Netherlands).…”

Section: Methodsmentioning

confidence: 99%

“…Extraction of cytosolic proteins from cultured cells and Western blot analysis were performed as described (14). Extraction of cytosolic proteins from tumor tissue was carried out according to Schunke et al (9). To visualize Rho-GDI· or Rho-GDIß protein the protein blot was incubated with a monoclonal mouse anti-Rho-GDI antibody or a rabbit polyclonal anti-D4-GDI antibody (BD Biosciences) at a dilution of 1:1000 or 1:5000, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemical staining of paraffinized breast cancer samples were carried out as described (9). Briefly, sections were deparaffinized by subsequent treatments with xylene (2x10 min), 100% ethanol (2x5 min), 96% ethanol (2x5 min), 70% ethanol (2x5 min).…”

Section: Methodsmentioning

confidence: 99%

“…In bladder and lung cancer, Rho-GDIß suppresses invasion and metastasis (5,6) and, in bladder cancer, high Rho-GDIß levels predict favorable prognosis (8). In breast cancer, Rho-GDIß is regulated by the oncoprotein Ets1 and has a dual function as it promotes the expression of the oncoprotein cyclooxygenase 2 (Cox-2) and, at the same time, inhibits cellular migration (9). Probably due to its dual function Rho-GDIß is not a suitable biomarker for predicting the outcome of breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Rho GDP dissociation inhibitor α expression correlates with the outcome of CMF treatment in invasive ductal breast cancer

Dittmer¹

2009

Int J Oncol

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Abstract. Rho-GDI· is an inhibitor of Rho-GTPases, which is involved in cancer progression. Little is known about its role in breast cancer progression. There is evidence, that Rho-GDI· may modulate drug resistance of breast cancer cells. To assess the importance of Rho-GDI· as a risk factor in invasive ductal breast cancer, cancer specimens of three groups of patients were analyzed for Rho-GDI· RNA (group 1, N=72 and group 2, N=73) or protein expression (group 3, N=90). In group 1, patients did not receive any adjuvant treatment, whereas, in groups 2 and 3, patients were treated with anti-estrogens and/or with chemotherapeutical drugs. Rho-GDI· RNA levels, measured by RT-PCR from freshfrozen material, did not correlate with relapse-free survival in Kaplan-Meier analysis, except in a subgroup of CMF-only treated patients. In this subgroup, higher Rho-GDI· RNA levels were significantly associated with more favorable prognosis. Immunohistochemical analysis (group 3) confirmed the link between higher Rho-GDI· expression and better outcome. This was again particularly true for the CMF-only treated patients. Cox regression analysis revealed that high Rho-GDI· protein expression reduced the risk for a relapse by ~3-fold, even if adjusted for grading, tumor size, nodal and estrogen receptor (ER) status. The data suggest that Rho-GDI· is beneficial to patients who received adjuvant chemotherapy. Rho-GDI· is possibly a useful biomarker to predict the response of breast cancer patients to CMF treatment.

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VEGF‐C mediates RhoGDI2‐induced gastric cancer cell metastasis and cisplatin resistance

Cho

Kim

Park

et al. 2014

Intl Journal of Cancer

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Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In this study, we clearly demonstrate that RhoGDI2 upregulates VEGF-C expression and RhoGDI2 expression is positively correlated with VEGF-C expression in human gastric tumor tissues as well as parental gastric cancer cell lines. VEGF-C depletion suppressed RhoGDI2-induced gastric cancer metastasis and sensitized RhoGDI2-overexpressing cells to cisplatin-induced apoptosis in vitro and in vivo. Secreted VEGF-C enhanced gastric cancer cell invasion and conferred cisplatin resistance to RhoGDI2-overexpressing cells. We also show that RhoGDI2 positively regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression suppressed RhoGDI2-induced VEGF-C expression, and this inhibition was associated with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2-overexpressing cells. Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer.Although the incidence and mortality of gastric cancer have steadily declined in recent decades, it remains the fourth most common cancer and the second leading cause of cancer mortality worldwide. 1

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Cox-2 is a target gene of Rho GDP dissociation inhibitor beta in breast cancer cells

Cited by 12 publications

References 0 publications

Association of D4-GDI expression with breast cancer progression

Association of D4-GDI expression with breast cancer progression

Rho GDP dissociation inhibitor α expression correlates with the outcome of CMF treatment in invasive ductal breast cancer

VEGF‐C mediates RhoGDI2‐induced gastric cancer cell metastasis and cisplatin resistance

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