دورية أكاديمية
RhoA: A therapeutic target for chronic myeloid leukemia
| العنوان: | RhoA: A therapeutic target for chronic myeloid leukemia |
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| المؤلفون: | Molli Poonam R, Pradhan Madhura B, Advani Suresh H, Naik Nishigandha R |
| المصدر: | Molecular Cancer, Vol 11, Iss 1, p 16 (2012) |
| بيانات النشر: | BMC |
| سنة النشر: | 2012 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Chronic Myeloid Leukemia (CML), Actin, RhoGTPases, Polymorphonuclear leukocytes (PMNL), n-formyl-methionyl-leucyl-phenylalanine (fMLP), Signal transduction, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Background Chronic Myeloid Leukemia (CML) is a malignant pluripotent stem cells disorder of myeloid cells. In CML patients, polymorphonuclear leukocytes (PMNL) the terminally differentiated cells of myeloid series exhibit defects in several actin dependent functions such as adhesion, motility, chemotaxis, agglutination, phagocytosis and microbicidal activities. A definite and global abnormality was observed in stimulation of actin polymerization in CML PMNL. Signalling molecules ras and rhoGTPases regulate spatial and temporal polymerization of actin and thus, a broad range of physiological processes. Therefore, status of these GTPases as well as actin was studied in resting and fMLP stimulated normal and CML PMNL. Methods To study expression of GTPases and actin, Western blotting and flow cytometry analysis were done, while spatial expression and colocalization of these proteins were studied by using laser confocal microscopy. To study effect of inhibitors on cell proliferation CCK-8 assay was done. Significance of differences in expression of proteins within the samples and between normal and CML was tested by using Wilcoxon signed rank test and Mann-Whitney test, respectively. Bivariate and partial correlation analyses were done to study relationship between all the parameters. Results In CML PMNL, actin expression and its architecture were altered and stimulation of actin polymerization was absent. Differences were also observed in expression, organization or stimulation of all the three GTPases in normal and CML PMNL. In normal PMNL, ras was the critical GTPase regulating expression of rhoGTPases and actin and actin polymerization. But in CML PMNL, rhoA took a central place. In accordance with these, treatment with rho/ROCK pathway inhibitors resulted in specific growth inhibition of CML cell lines. Conclusions RhoA has emerged as the key molecule responsible for functional defects in CML PMNL and therefore can be used as a therapeutic target in CML. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1476-4598 |
| العلاقة: | http://www.molecular-cancer.com/content/11/1/16Test; https://doaj.org/toc/1476-4598Test; https://doaj.org/article/1bd04309874f480cab7858a967aed29aTest |
| DOI: | 10.1186/1476-4598-11-16 |
| الإتاحة: | https://doi.org/10.1186/1476-4598-11-16Test https://doaj.org/article/1bd04309874f480cab7858a967aed29aTest |
| رقم الانضمام: | edsbas.789AF108 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14764598 |
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| DOI: | 10.1186/1476-4598-11-16 |