Inactivation of CHEK1 and EI24 is Associated with the Development of Invasive Cervical Carcinoma: Clinical and Prognostic Implications
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Inactivation of CHEK1 and EI24 is Associated with the
Development of Invasive Cervical Carcinoma: Clinical
and Prognostic Implications
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| Creator |
Mazumder, Dipanjana
Mitra, Sraboni Singh, Ratnesh Kumar Dutta, Sankhadeep Roy, Anup Mondal, Ranajit Kumar Basu, Partha Sarathi Roychoudhury, Susanta Panda, Chinmay Kumar |
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| Subject |
Molecular & Human Genetics
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| Description |
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.
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| Publisher |
John Wiley & Sons
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| Date |
2011
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/3/1/te1.pdf
Mazumder, Dipanjana and Mitra, Sraboni and Singh, Ratnesh Kumar and Dutta, Sankhadeep and Roy, Anup and Mondal, Ranajit Kumar and Basu, Partha Sarathi and Roychoudhury, Susanta and Panda, Chinmay Kumar (2011) Inactivation of CHEK1 and EI24 is Associated with the Development of Invasive Cervical Carcinoma: Clinical and Prognostic Implications. International Journal of Cancer, 129. pp. 1859-1871. ISSN 0020-7136 |
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| Relation |
http://dx.doi.org/10.1002/ijc.25849
http://www.eprints.iicb.res.in/3/ |
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