cDNA expression array reveals heterogeneous gene expression profiles in three glioblastoma cell lines

Rhee, Chang Hun; Hess, Kenneth R.; Jabbur, James R.; Ruiz, Maribelís; Yu, Yang; Chen, Stephen; Chenchik, Alex; Fuller, Gregory N.; Zhang, Wei

doi:10.1038/sj.onc.1202623

Cited by 53 publications

(25 citation statements)

References 8 publications

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“…Microarray studies revealed that in each type of tumor cells, more than one hundred genes exhibited abnormal expression or mutation (25). Thus, finding the key genes that participate in or regulate the tumorigenesis process has become an important task in cancer research.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Tao

et al. 2012

Oncol Rep

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Abstract. Chemotherapy is widely used for the treatment of glioma. Given the high resistance of brain neoplasm tissues to chemotherapy, it is important to find new methods to improve the effects of chemotherapy. However, the molecular mechanisms underlying glioma resistance to chemotherapy are largely unknown. Here, we demonstrate that CDK6, a cell cycle regulator, is significantly upregulated in glioma cells, and the increasing expression of CDK6 correlates well with the grades of glioma malignancy. Using shRNA-mediated CDK6 knockdown, we found that the proliferation and survival of tumor cells were dramatically inhibited. Moreover, CDK6 knockdown in the U251 glioma cell line caused significant increase in the apoptosis of U251 cells treated with temozolomide (TMZ). Furthermore, CDK6 knockdown reduced the expression level of drug resistance genes such as MRP and MDR. These data indicate that CDK6 is an important mediator of glioma resistance to chemotherapy. Our findings provide a new strategy for the development of chemotherapy sensitizer. IntroductionGlioma is the most common tumor of the brain and accounts for 45-55% of all brain tumors. Based on histological features (nuclear atypia, mitosis, microvascular enrichment and necrosis) and malignancy, glioma is classified into four grades (1). Grade 1 is innocent and curable with surgical resection; grade 2 is a low grade diffuse glioma and can progress into higher grades; grade 3 and 4 gliomas are malignant and have increased capability to proliferate and invade. The grade 4 glioma, glioblastoma multiforme (GBM), is the most aggressive.Surgical resection is the primary therapy to treat glioma (2). However, surgical removal is very restrictive, thus it is difficult to completely remove diffusive tumor tissues, especially higher grade gliomas. These glioma tissues invade into the white matter or diffuse along the ventricle surface, so other strategies such as chemotherapy are very important to remove cancer cells as completely as possible (3-5). Chemotherapy increases the life of GBM patients. Clinical statistics reveals that, chemotherapy treatment leads to a 15% reduction of mortality, and a 6% increase of 1-more year survival. However, the effect of chemotherapy on glioma is not satisfactory, largely due to three problems. The first problem is the diagnosis of diffusive glioma tissues, which are tiny and grow deep in the brain tissue and are hard to access. The second problem is the blockade of chemotherapy drug by the blood-brain barrier. The third problem is that glioma is highly tolerant under chemotherapy treatment. Understanding the fundamentals, especially the molecular mechanisms, is critical to increase the susceptibility of glioma to chemotherapy.Tumor cells originated from cells with abnormal proliferation and dysregulation of the cell cycle (6,7). Molecular profiling studies showed that the genes controlling cell growth and restricting cell division are silenced, and genes promoting cell proliferation and facilitating cell cycle are overexpressed. M...

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Section: Discussionmentioning

confidence: 99%

Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Tao

et al. 2012

Oncol Rep

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“…44,65,66 On BFM studies, patients with t(9;22)(q34;q11) or t(4;11) (q21;q23) and a good 'prednisone' response have a better outcome than patients with the same translocation and a poor prednisone response. 67,68 Micro-array technology 69,70 may help us move to a multimarker classification scheme to match the complex heterogeneity of childhood ALL.…”

Section: Discussionmentioning

confidence: 99%

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995

et al. 2000

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Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983-1988 and 1989-1995). Overall, 10-year EFS was 62% ± 10% for the 1983-1988 series and 72% ± 1% for the 1988-1995 series (P Ͻ 0.0001). Five-year cumulative rates of isolated CNS relapses were 5.9% and 4.4%. Therapy based on the Berlin-Frankfurt-Mü nster 76/79 study improved outcomes for intermediate and higher risk patients in the first series. For intermediate risk patients, delayed intensification (DI) was most crucial for improved outcome and cranial irradiation was safely replaced with maintenance intrathecal methotrexate, providing patients received intensified systemic therapy. In the second series, randomized trials showed better outcome with one vs no DI phase for lower risk patients, with two vs one DI phase for intermediate risk patients, and with the CCG 'augmented regimen' for higher risk patients with a slow day 7 marrow response. Cranial irradiation was safely replaced with additional intrathecal methotrexate for higher risk patients with a rapid day 7 marrow response. In a subsequent study, substitution of dexamethasone in place of prednisone in induction and maintenance improved outcome for standard risk patients. All patients received dexamethasone in DI. These successful treatment strategies form the basis for our current ALL trials. Leukemia (2000) 14, 2223-2233.

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“…The signal of housekeeping genes such as GAPDH or ␤-actin was chosen as reference for normalization, and the total signal amount of the membranes were also applied as reference. The ratio of each gene's signal to that of GAPDH on the same filter was chosen to compare the relative expression levels between cell lines (Pietu et al 1999;Rhee et al 1999). The publication costs of this article were defrayed in part by payment of page charges.…”

Section: Signal Detection and Gene Expression Quantificationmentioning

confidence: 99%

Cloning and Functional Analysis of cDNAs with Open Reading Frames for 300 Previously Undefined Genes Expressed in CD34+ Hematopoietic Stem/Progenitor Cells

Zhang

Yang

Wu³

et al. 2000

Genome Res.

165

127

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Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3Ј UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.

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cDNA expression array reveals heterogeneous gene expression profiles in three glioblastoma cell lines

Cited by 53 publications

References 8 publications

Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995

Cloning and Functional Analysis of cDNAs with Open Reading Frames for 300 Previously Undefined Genes Expressed in CD34+ Hematopoietic Stem/Progenitor Cells

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