Small G‐protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis

Bektic, Jasmin; Pfeil, Karina; Berger, Andreas; Ramoner, Reinhold; Pelzer, Alexandre; Schäfer, Georg; Kofler, Kurt; Bartsch, Georg; Klocker, Helmut

doi:10.1002/pros.20243

Cited by 74 publications

(74 citation statements)

References 24 publications

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“…A recent report found complete loss of expression or reduced expression of RhoE in prostate cancer compared with the benign prostate. 16 Another research also showed that RhoE gene was amplified 9.44-fold in the epithelial cell of the parous breast compared with that of nulliparous breast. 19 Considering that RhoE may play a role in carcinogenesis through changes of expression, in this study, we examined RhoE expressions both quantitatively and qualitatively in a sample of 30 lung cancer tissues and the background lung tissues.…”

Section: Discussionmentioning

confidence: 97%

“…Furthermore, restoration of RhoE expression in prostate cancer cells inhibits cancer cell growth and results in G 2 /M arrest, indicating RhoE may act as a tumor suppressor. 16 On the other hand, the levels of RhoE expression are significantly higher in the prostate cancer cell lines with high metastatic potential compared with those with low metastatic potential, 17 suggesting a role for RhoE in metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of RhoE in non-small cell lung cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes

Zhang¹,

Hu²,

Zhou³

et al. 2007

Cancer Biology & Therapy

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RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p < 0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p < 0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p < 0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Overexpression of RhoE in non-small cell lung cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes

Zhang¹,

Hu²,

Zhou³

et al. 2007

Cancer Biology & Therapy

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“…Using a combination of cell culture, ex vivo, and in vivo approaches, we have identified evidence supporting that Rnd3 has barrier‐protective properties under certain conditions, such as following acute inflammatory challenge. The involvement of Rnd3 in the control of endothelial barrier function adds to a growing list of recently described functions ascribed to Rnd family proteins, including Ca 2+ homeostasis in the heart,53 regulation of Notch1 signaling,54 control of cell cycle progression,55, 56, 57 development of the central nervous system,58, 59, 60 control of cell motility and metastatic potential of certain cancers,29, 61, 62, 63, 64 and a potential role in cardioprotection against heart failure 65. In addition, we provide novel evidence that delivery of Rnd3 protein can serve as a potential therapeutic tool to ameliorate microvascular hyperpermeability caused by tissue injury.…”

Section: Discussionmentioning

confidence: 99%

Rnd3 as a Novel Target to Ameliorate Microvascular Leakage

Breslin

Daines

Doggett

et al. 2016

JAHA

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BackgroundMicrovascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.Methods and ResultsUsing immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate–albumin and transendothelial electrical resistance of human umbilical vein endothelial cell monolayers served as indices of barrier function, and RhoA, Rac1, and Cdc42 activities were determined using G‐LISA assays. Overexpression of Rnd3 significantly reduced the magnitude of thrombin‐induced barrier dysfunction, and abolished thrombin‐induced Rac1 inactivation. Depleting Rnd3 expression with siRNA significantly extended the time course of thrombin‐induced barrier dysfunction and Rac1 inactivation. Time‐lapse microscopy of human umbilical vein endothelial cells expressing GFP‐actin showed that co‐expression of mCherry‐Rnd3 attenuated thrombin‐induced reductions in local lamellipodia that accompany endothelial barrier dysfunction. Lastly, a novel Rnd3 protein delivery method reduced microvascular leakage in a rat model of hemorrhagic shock and resuscitation, assessed by both intravital microscopic observation of extravasation of fluorescein isothiocyanate–albumin from the mesenteric microcirculation, and direct determination of solute permeability in intact isolated venules.ConclusionsThe data suggest that Rnd3 can shift the balance of RhoA and Rac1 signaling in endothelial cells. In addition, our findings suggest the therapeutic, anti‐inflammatory potential of delivering Rnd3 to promote endothelial barrier recovery during inflammatory challenge.

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“…KRT18 is a cytokeratin known to be expressed in the umbrella layer of urothelium whose expression increases with urothelial carcinogenesis [25]. ARHE (also 'Rho family GTPase 3' (RND3)) is a Rho signal transduction member with roles in many cellular processes (cytoskeleton organization, membrane trafficking, cell growth and apoptosis) [29], whose loss is reported in prostate cancer. Deranged DNA repair is represented by BRCA2 and LIG3 [30].Whilst neither is directly linked with bladder carcinogenesis, it is possible that loss of both is required for carcinogenic alteration.…”

Section: Discussionmentioning

confidence: 99%

The Application of Artificial Intelligence to Microarray Data: Identification of a Novel Gene Signature to Identify Bladder Cancer Progression

et al. 2010

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Small G‐protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis

Abstract: In conclusion, our findings suggest RhoE as a tumor suppressor gene that is downregulated early in the development of prostate cancer.

Cited by 74 publications

References 24 publications

Overexpression of RhoE in non-small cell lung cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes

Overexpression of RhoE in non-small cell lung cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes

Rnd3 as a Novel Target to Ameliorate Microvascular Leakage

The Application of Artificial Intelligence to Microarray Data: Identification of a Novel Gene Signature to Identify Bladder Cancer Progression

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