Differential expression ofHOX genes in neoplastic and non-neoplastic human astrocytes

Abdel-Fattah, Rana; Xiao, Aizhen; Bomgardner, Daniela; Pease, Clinton S.; Lopes, M. Beatriz; Hussaini, Isa M.

doi:10.1002/path.1939

Cited by 58 publications

(52 citation statements)

References 31 publications

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“…The effect of BA treatment on invasive tendency in U-118 and U-138 glioma cell lines was also studied. The results from RT-PCR analysis revealed expression of 26/39 HOX genes in NHAs in agreement with an earlier study (28). HOX A6, A7, A9, A13, B13, C6, C8, C10, D1, D4, D9, D10, and D13 were all silent in the NHA cell line.…”

Section: Discussionsupporting

confidence: 79%

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Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma

Guo

Shao²,

Chen

et al. 2015

Oncology Letters

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Abstract. Transcription factors encoded by HOX genes are vital in the determination of cell fate and identity during embryonic development. In certain malignancies, HOX genes also behave as oncogenes. The present study demonstrated suppression of the invasive tendency of glioblastoma multiforme U-118 and U-138 cells by the introduction of the antisense fragments of HOXA6 and B13 genes using electroporation. The invasion index indicated 79 and 72% reductions in the invasive ability of antisense HOXA6 and B13, respectively. No significant differences in the invasive index of the parental and mock cells of each HOX gene were observed (invasive index, 0.75-0.91; P=0.05). A reduction in invasion tendency was also observed following betulinic acid (BA) treatment: The results from the matrigel assay analysis clearly demonstrated a significant inhibition in the invasive behaviour of U-118 and U-138 cell lines from day 15 following BA treatment, with a maximum effect on day 30. The invasion index demonstrated 62 and 65% reductions in invasion ability in the U-118 and U-138 cell lines, respectively. The suppression of HOXC6 and B13 expression by the introduction of the corresponding antisense fragments in addition to BA reduced invasion tendency in U-118 and U-138 cell lines. The mechanism underlying the association between the HOX gene and invasive behavior in glioma cells is yet to be understood. However, the anti-invasive behavior of BA may aid understanding of the mechanism in future studies.

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Section: Discussionsupporting

confidence: 79%

“…Previously, it was reported that HOXD genes were expressed in neoplastic astrocytes (21) and pediatric low-grade gliomas (22). However, little is known about the function of HOXD genes, particularly in gliomas.…”

Section: Introductionmentioning

confidence: 99%

Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma

Guo

Shao²,

Chen

et al. 2015

Oncology Letters

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“…Direct detection of the PCR product was monitored by measuring the increase in fluorescence caused by the binding of SYBR Green to dsDNA as described previously. 30 …”

Section: Real-time Pcrmentioning

confidence: 99%

Matrix Metalloproteinase-9 Is Differentially Expressed in Nonfunctioning Invasive and Noninvasive Pituitary Adenomas and Increases Invasion in Human Pituitary Adenoma Cell Line

Hussaini

Trotter

Zhao

et al. 2007

The American Journal of Pathology

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The complete resection of pituitary adenomas (PAs) is unlikely when there is an extensive local dural invasion and given that the molecular mechanisms remain primarily unknown. DNA microarray analysis was performed to identify differentially expressed genes between nonfunctioning invasive and noninvasive PAs. Gene clustering revealed a robust eightfold increase in matrix metalloproteinase (MMP)-9 expression in surgically resected human invasive PAs and in the (nonfunctioning) HP75 human pituitary tumorderived cell line treated with phorbol-12-myristate-13-acetate; these results were confirmed by real-time polymerase chain reaction, gelatin zymography, reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and Northern blot analyses. The activation of protein kinase C (PKC) increased both MMP-9 activity and expression, which were blocked by some PKC inhibitors (Gö6976, bisindolylmaleimide, and Rottlerin), PKC-␣, and PKC-␦ small interfering (si)RNAs but not by hispidin (PKC-␤ inhibitor). In a transmembrane invasion assay, phorbol-12-myristate-13-acetate (100 nmol/L) increased the number of invaded HP75 cells, a process that was attenuated by PKC inhibitors, MMP-9 antibody, PKC-␣ siRNA, or PKC-␦ siRNA. These results demonstrate that MMP-9 and PKC-␣ or PKC-␦ may provide putative therapeutic targets for the control of PA dural invasion. (Am J

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“…19 During normal morphogenesis, HOXD13 is involved in the determination of the terminal digestive and urogenital tracts. [20][21][22] HOXD13 deregulation has been further detected in different tumor types, such as breast cancer, melanoma, cervical cancer and atrocytomas, [23][24][25][26] and in the neuro-endocrine differentiation of human advanced prostate cancers. 27 Here, to immunohistochemically detect the expression of HOXD13 homeoprotein in normal tissues and its potential deregulation along the evolution of specific tumor types, we utilized tissue microarrays (TMAs) including >4,000 different normal tissue and cancer sample types from 79 different tumor categories.…”

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confidence: 99%

HOX D13 expression across 79 tumor tissue types

Cantile

Franco

Tschan

et al. 2009

Intl Journal of Cancer

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HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas-tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis. ' UICCKey words: HOXD13; HOX and multitumor tissue microarray; HOXD13 and pancreas Class I Homeobox genes (Hox, mice; HOX, human) are transcription factors mostly involved in embryonic development. 1 They display an unique genomic network organization: 4 compact chromosomal loci (HOXA at 7p15.3, HOXB at 17q21.3, HOXC at 12q13.3 and HOXD at 2q31 2 ) where 39 sequence corresponding genes can be aligned with each other into 13 antero-posterior paralogous groups. The HOX gene network, the most repeat-poor regions in the human genome, 3 is also expressed in normal adult human organs. 4 HOX genes appear to regulate phenotype cell identity, 5,6 cell differentiation 7,8 and control primary cellular processes, as proven by the description of congenital, 9 somatic 10 and metabolic 11 diseases involving these genes. Furthermore, besides the already established role of the HOX network in hematopoiesis and leukemogenesis, 12 HOX genes are implicated in the neoplastic alterations of human solid tissues and organs such as kidney, colon, lung, skin, bladder, liver, breast and prostate. 13,14 New crucial functions have recently been ascribed to HOX genes and homeoproteins mostly related to their interaction with miRNAs and ncRNAs to guarantee transcription and export of specific mRNAs. 15,16 Locus D HOX genes are localized on chromosome 2q31-32 and play a role, with its posterior paralogous genes, in limb and digit generation during embryonic development 1...

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Differential expression ofHOX genes in neoplastic and non-neoplastic human astrocytes

Cited by 58 publications

References 31 publications

Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma

Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma

Matrix Metalloproteinase-9 Is Differentially Expressed in Nonfunctioning Invasive and Noninvasive Pituitary Adenomas and Increases Invasion in Human Pituitary Adenoma Cell Line

HOX D13 expression across 79 tumor tissue types

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