Loss of putative tumor suppressor EI24/PIG8 confers resistance to etoposide

Mork, Christina N.; Faller, Douglas V.; Spanjaard, Remco A.

doi:10.1016/j.febslet.2007.10.046

Cited by 32 publications

(27 citation statements)

References 14 publications

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“…LTBR, a proapoptotic gene, was down-regulated in busulfan-resistant human myeloid leukemia cells compared to sensitive cells [50]. EI24, a p53-target gene, was lost in invasive breast cancers, and knockdown of EI24 conferred resistance to etoposide treatment in breast cancer cells [51]. SMAD2 expression is lower in glioma cells than in normal astrocytes [52].…”

Section: Discussionmentioning

confidence: 98%

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

Ujifuku¹,

Mitsutake²,

Takakura³

et al. 2010

Cancer Letters

209

137

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Running title: miRNAs and temozolomide resistance in glioblastoma Key words: glioblastoma, resistance, microRNA,, miR-10a*, temozolomide. ABSTRACTTo identify microRNAs (miRNAs) specifically involved in the acquisition of temozolomide (TMZ) resistance in glioblastoma multiforme (GBM), we first established a resistant variant, U251R cells from TMZ-sensitive GBM cell line, U251MG. We then performed a comprehensive analysis of miRNA expressions in U251R and parental cells using miRNA microarrays. miR-195, miR-455-3p and miR-10a* were the three most up-regulated miRNAs in the resistant cells. To investigate the functional role of these miRNAs in TMZ resistance, U251R cells were transfected with miRNA inhibitors consisting of DNA/LNA hybrid oligonucleotides. Suppression of miR-455-3p or miR-10a* had no effect on cell growth, but showed modest cell killing effect in the presence of TMZ. On the other hand, knockdown of miR-195 alone displayed moderate cell killing effect, and combination with TMZ strongly enhanced the effect. In addition, using in silico analysis combined with cDNA microarray experiment, we present possible mRNA targets of these miRNAs. In conclusion, our findings suggest that those miRNAs may play a role in acquired TMZ resistance and could be a novel target for recurrent GBM treatment.

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Section: Discussionmentioning

confidence: 98%

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

Ujifuku¹,

Mitsutake²,

Takakura³

et al. 2010

Cancer Letters

209

137

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“…42 Increase in expression of EI24 by etoposide treatment has been reported in in vitro systems. 22,43 However, suppression of EI24 mRNA level inhibits etoposide-induced apoptosis. 43 Unlike us, Zhang et al 7 showed no significant difference in expression of LOH11CR2A in normal cervix and CACX by semiquantitative RT-PCR.…”

Section: Reduction In Mrna Expression Of the Candidate Tsgsmentioning

confidence: 99%

“…22,43 However, suppression of EI24 mRNA level inhibits etoposide-induced apoptosis. 43 Unlike us, Zhang et al 7 showed no significant difference in expression of LOH11CR2A in normal cervix and CACX by semiquantitative RT-PCR. Low expression of LOH11CR2A transcripts by Northern blot analysis was found in breast, ovarian and lung cancer cell lines.…”

Section: Reduction In Mrna Expression Of the Candidate Tsgsmentioning

confidence: 99%

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

Mazumder

Mitra

Singh

et al. 2011

Intl Journal of Cancer

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To understand the importance of frequent deletion of chromosomal 11q23.3-24.3 region in cervical carcinogenesis, alterations (deletion/methylation/mutation/expression) of the candidate genes LOH11CR2A, EI24 and CHEK1 located in the region were analyzed in 29 cervical intraepithelial neoplasia (CIN), 112 cervical carcinoma (CACX) samples and two CACX cell lines. The deletion frequency of these genes was low in CIN than in CACX [CIN: CHEK1: 28%, EI24: 21%, LOH11CR2A: 15% and CACX: CHEK1: 51%, EI24: 41%, LOH11CR2A: 36%]. Similar trend was seen in promoter methylation of these genes [CIN: CHEK1: 10%, EI24: 3%, LOH11CR2A: 3% and CACX: CHEK1: 55%, EI24: 31%, LOH11CR2A: 14%]. Mutations of the genes are a rare event. Overall alterations (deletion and methylation) of CHEK1 and EI24 were associated with progression of CACX. Quantitative mRNA expression analysis showed reduced expression of the three genes in concordance to their molecular alterations. A shorter isoform of CHEK1 lacking exon 8, hence impaired in substrate binding capacity, was found in two samples. Immunohistochemical analysis showed nuclear expression of Chek1, p-Chek1 and Ei24 in tumor tissues, whereas the cell lines exhibited both nuclear and cytoplasmic expression of Chek1 and Ei24, as is also evident from Western blot analysis suggesting differential localization of the proteins. Alterations of CHEK1 and EI24 coupled with tumor stage and early sexual debut ( 19 years) predicted worst prognosis. Thus, our data suggest that inactivation of EI24 and CHEK1 through two independent mechanisms contributes to the development of CACX.Worldwide, cervical cancer (CACX) is one of the most deadly cancers among women and occupies second position among females in eastern India (Kolkata). 1 Infection by highrisk human papillomavirus (HPV) is a major cause of CACX 2 along with other etiological factors, such as use of oral contraceptives, precocious marriage, multiparity and smoking. 1,3 As HPV infections in most cases do not lead to cancer, and even a long latency period for the cancerous outcome in infected women suggests involvement of additional genetic alterations like functional inactivation of tumor suppressor genes (TSGs) or activation of oncogenes. 4 Investigations showing frequent chromosomal deletion in 11q23-q24 (20.4 Mb) in cervix, 5-7 breast, 8,9 lung, 10 colon 11 and ovarian 12 cancer and functional chromosome-transfer

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“…Overexpression of Ei24 suppresses cell growth and induces apoptosis, while depletion of Ei24 results in suppression of apoptosis in response to pro-apoptotic treatment (2)(3)(4). The human EI24 gene is located on chromosome 11q23, a region frequently displaying loss of heterozygosity in several malignancies, including invasive cervical cancers, breast carcinomas and malignant melanoma (5).…”

mentioning

confidence: 99%

The p53-induced Gene Ei24 Is an Essential Component of the Basal Autophagy Pathway

Zhao

et al. 2012

Journal of Biological Chemistry

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Background:The function of the p53-induced gene Ei24 in the autophagy pathway remains largely unknown. Results: Ei24 deficiency impairs autophagic flux. Mice deficient in Ei24 show massive neuron degeneration and severe liver injury. Conclusion: Ei24 functions in basal autophagy in clearance of aggregate-prone proteins in neurons and hepatocytes. Significance: We revealed that EI24 is an essential component of the basal autophagy pathway.

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Loss of putative tumor suppressor EI24/PIG8 confers resistance to etoposide

Cited by 32 publications

References 14 publications

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: Clinical and prognostic implications

The p53-induced Gene Ei24 Is an Essential Component of the Basal Autophagy Pathway

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