The
            <i>BCSC-1</i>
            locus at chromosome 11q23-q24 is a candidate tumor suppressor gene

Martin, Eric S.; Cesari, Rossano; Pentimalli, Francesca; Yoder, Kristine E.; Fishel, Richard; Himelstein, Andrew L.; Martín, Sabrina; Godwin, Andrew K.; Negrini, Massimo; Croce, Carlo M.

doi:10.1073/pnas.1934602100

Cited by 48 publications

(67 citation statements)

References 28 publications

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“…However, comparable deletion frequency of LOH11CR2A was observed for carcinomas of breast (44%, 7/16) and ovary (38%, 5/13). 18 In between D1 and D2 regions, there are two more overlapping candidate genes ROBO3 and ROBO4 (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…Low expression of LOH11CR2A transcripts by Northern blot analysis was found in breast, ovarian and lung cancer cell lines. 18 On the contrary, high expression of this gene was found in CNE-2L2 human nasopharyngeal carcinoma cells by microarray analysis. 44 Ectopic expression of Loh11cr2a enhanced cellular aggregation and increased the expression of E-cadherin/a-catenin, 44 thus suggesting its tumor suppressive activity.…”

Section: Reduction In Mrna Expression Of the Candidate Tsgsmentioning

confidence: 96%

“…However, in breast, lung and ovarian cancers, the prevalence of major alleles of the SNPs was reported, though the sample size was very low. 16,18 Mutation screening of other exons of the genes is required to locate the mutation hotspot, if any.…”

Section: Mutation Is a Rare Event For Chek1 Ei24 And Loh11cr2amentioning

confidence: 99%

“…17 Several nonsynonymous SNPs in exons 12, 14 and 17 of LOH11CR2A have been detected in breast, lung and ovarian cancer patients. 16,18 PTT analysis revealed 9% mutation of this gene in breast cancer. 19 However, no such association of LOH11CR2A with CACX has yet been reported.…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Reduction In Mrna Expression Of the Candidate Tsgsmentioning

confidence: 96%

Section: Mutation Is a Rare Event For Chek1 Ei24 And Loh11cr2amentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…This tumor suppressor is mutated in a large fraction of various human tumors (18), but its sequence has not revealed anything about how it might work to control cell cycle progression or cell growth. Overexpression of BCSC-1 in oocytes by mRNA injection with or without mutation of conserved consensus PKA phosphorylation sites has not shown a consistent effect on progesteroneinduced oocyte maturation to date, which might be expected for a tumor suppressor already expressed at high levels in the cell.…”

Section: Role Of Pka In Oocyte Maturationmentioning

confidence: 99%

Pioneering the Xenopus Oocyte and Egg Extract System

Maller

2012

Journal of Biological Chemistry

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Getting Started: Selecting Xenopus Oocytes as a Model SystemA Reflections article provides an opportunity to focus on key findings during a career from a personal and historical perspective. As a graduate student in the late 1960s at Berkeley, I was introduced to the Xenopus oocyte by John Gerhart, who shared his fascination with the work of John Gurdon, who had pointed out the unique and powerful features of the oocyte and egg, particularly the ability to microinject biochemically significant amounts of material into them while they carried out complex biological events. This approach using the oocyte as a living biochemical test tube long predated the age of cloning and gene transfection. Later, the synchronous, hormone-stimulated transition of the oocyte from G 2 to M phase during maturation encouraged a focus on cell cycle control. Key events over the years include identifying changes in protein phosphorylation as the initiating signal for oocyte maturation and, more universally, for the action of maturation-promoting factor (MPF) to drive cells into M phase. A crucial advance came from developing methods to produce large quantities of concentrated egg extracts that could carry out MPF-dependent cell cycle transitions, DNA replication, and other complex processes in vitro. M phase phosphorylation analysis led to purification of p90RSK and the discovery of the MAPK pathway, which underlies many biological events, including the metaphase arrest of the unfertilized egg. A seminal breakthrough came from purifying MPF from egg extracts and showing that it was a complex of the Cdc2 kinase and cyclin B, uniting the genetic and biochemical approaches to cell cycle control. The oocyte and egg extract system continues to provide new insight into many areas of biology, including the action of other mitotic kinases and centrosome duplication. The unique and powerful features of the Xenopus system hold great promise for more work and insight into fundamental problems of biology and medicine. Early EducationAs an undergraduate in biochemistry at Cornell University, I found that I liked both organic chemistry and biology. I had to work my way through college and knew that I wanted to go to graduate school in an environment totally different from upstate New York and in a program where students would have full support for their studies. I had heard about the new field of molecular biology and was accepted into one of the first programs in that area, at the University of California, Berkeley. I arrived in Berkeley in early 1969 just after the People's Park demonstrations and was entranced by the high intensity of life, science, politics, and food and the beauty of the mountains and the sea.After doing rotations in several laboratories, I realized that nearly all students in the department were working on the properties of a single molecule isolated from a bacterial cell, and I wanted to find a laboratory or project with more relevance to actual cell physiology. At that time, John Gerhart, famous for discovering feedback inhi...

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