Evidence for a Tumour Suppressive Function of APRG1 in Breast Cancer

Leris, A.C.A.; Roberts, Timothy; Jiang, Wen Guo; Newbold, RF; Mokbel, Kefah

doi:10.1007/s10549-005-4169-z

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…25 APRG1 was suggested to have tumor suppression function in breast cancer. 26 This gene encodes a putative protein of 170 amino acids (isoform B), which has an N-terminal part conserved among members of the eukaryotic translation factor 6 gene family. The analysis by PROSITE, the database of protein domains, families and functional sites, had revealed peptide patterns corresponding to the cell attachment sequence Arg-Gly-Asp, which suggests The majority of the corresponding genes is located on 3p, the short arm of chromosome 3.…”

Section: Discussionmentioning

confidence: 99%

Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer

et al. 2013

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“…( 24 ) The APRG1 gene located 0.4 Mb centromeric to hMHL1 has been implicated in cell membrane interactions and reported to be a candidate TSG associated with BC. ( 25 ) Another candidate TSG, ITGA9 (integrin α9 subunit) gene located 0.4 Mb further down‐stream of APRG1 , is a member of the β1 integrin family expressed by stratified squamous epithelium and associated with cell differentiation and growth. ( 26 ) The RBSP3/HYA22 ( CTDSPL ) gene located 190 kilobase (Kb) downstream of ITGA9 was reported to undergo frequent homozygous (HD) and hemizygous deletion (HED) in various malignancies including BC.…”

mentioning

confidence: 99%

Frequent alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 region in early and late‐onset breast carcinoma: clinical and prognostic significance

et al. 2008

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Young age can be an independent prognostic factor for adverse prognosis in women with breast carcinoma (BC). In younger women, BC exhibited more aggressive pathological features than older women, indicating differences in biology. Frequent alterations in chromosomal (chr.) 3p22.3 in different malignancies indicated the existence of multiple candidate tumor suppressor genes (TSG) in this region, yet its association with BC remains unclear. In an effort to understand the differences in molecular pathogenesis in two age groups of BC, detailed analysis of alterations at chr.3p22.3 region was carried out in 47 early onset (group-A: 40 years) and 59 lateonset (group-A: >40 years) BC samples. Deletion mapping of the four candidate TSG, hMLH1, APRG1, ITGA9 and RBSP3/HYA22, located within 1 Mb of chr.3p22.3 showed high deletion in hMLH1 and RBSP3/HYA22 genes. Frequent methylation was also observed in these genes and significantly associated with their deletion. Quantitative messenger RNA (mRNA) expression and immunohistochemical analysis showed down-regulation of these genes. Alterations (deletion/methylation) of hMLH1 were significantly associated with RBSP3/HYA22 in group-A (P = 0.02). Significant poor survival in group-A patients with alterations in hMLH1 and RBSP3/ HYA22 and the same in group-B patients with hMLH1 alterations indicated their importance as prognostic markers. Differential association of alterations of these genes with higher histological grades, more advanced stages and positive lymph node involvement were also seen. Thus, the present study suggests hMLH1 and RBSP3/HYA22 to be candidate TSG associated with development of both early and late-onset BC undergoing frequent genetic and epigenetic alteration and having significant prognostic implications. (Cancer Sci 2008; 99: 1984-1991 B reast cancer (BC), is the third most prevalent malignancy and primary cause of death in women worldwide.(1) In India, it accounts for 19% of all cancers among women, and is the second most common cancer when both sexes are considered together, whereas about 23% of eastern Indian women suffer from this disease. (2,3) Considering the age at onset of tumor, BC can be classified as early onset (group-A: ≤40 years) and late-onset (group-B: >40 years).(4,5) However, the cut-off value for early onset BC varies among investigators, ranging from 35-50 years. (6,7) Despite this discrepancy, younger women with BC exhibit more aggressive pathological features, including large tumor size of higher grade, presence of positive lymph nodes, absence of steroid receptors and high S-phase fraction, than older women with BC.(6,7) Another report showed that, in an Asian population, BC patients below 40 years have tumors with a poorer prognostic profile. However, this did not translate into poorer overall survival and might be attributable to more aggressive adjuvant treatment of younger patients.(8) All these reports suggested early onset BC to be a biologically separate disease that independently predicts more adverse outcomes. Thus, the mol...

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“…Reduced expression may be associated with gestational diabetes while high expression may be associated with poor prognosis in hepatocellular carcinoma (44). C3orf35 is an alias and previous HGNC symbol for the APRG1 tumor suppressor candidate which is an RNA gene with little known properties or associations beyond a study in 2005 that it may suppress tumor growth in breast cancer (45). The protein from Sprouty RTK Signaling Antagonist 2 (SPRY2) is involved in the noncell autonomous inhibitory effect on fibroblast growth factor two signaling.…”

Section: Discussionmentioning

confidence: 99%

Translating genetic findings to epigenetics: identifying the mechanisms associated with aging after high-radiation exposure on earth and in space

Ruprecht,

Singhal,

Sens

et al. 2024

Front. Public Health

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PurposeExposure to radiation is a health concern within and beyond the Earth's atmosphere for aircrew and astronauts in their respective austere environments. The biological effects of radiation exposure from a multiomics standpoint are relatively unexplored and stand to shed light on tailored monitoring and treatment for those in these career fields. To establish a reference variable for genetic damage, biological age seems to be closely associated with the effect of radiation. Following a genetic-based study, this study explores the epigenetic landscape of radiation exposure along with its associative effects on aging processes.MethodsWe imported the results of the genetics-based study that was a secondary analysis of five publicly available datasets (noted as Data1). The overlap of these genes with new data involving methylation data from two datasets (noted as Data2) following similar secondary analysis procedures is the basis of this study. We performed the standard statistical analysis on these datasets along with supervised and unsupervised learning to create preranked gene lists used for functional analysis in Ingenuity Pathway Analysis (IPA).ResultsThere were 664 genes of interest from Data1 and 577 genes from Data2. There were 40 statistically significant methylation probes within 500 base pairs of the gene's transcription start site and 10 probes within 100 base pairs, which are discussed in depth. IPA yielded 21 significant pathways involving metabolism, cellular development, cell death, and diseases. Compared to gold standards for gestational age, we observed relatively low error and standard deviation using newly identified biomarkers.ConclusionWe have identified 17 methylated genes that exhibited particular interest and potential in future studies. This study suggests that there are common trends in oxidative stress, cell development, and metabolism that indicate an association between aging processes and the effects of ionizing radiation exposure.

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Evidence for a Tumour Suppressive Function of APRG1 in Breast Cancer

Cited by 6 publications

References 8 publications

Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer

Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer

Frequent alterations of hMLH1 and RBSP3/HYA22 at chromosomal 3p22.3 region in early and late‐onset breast carcinoma: clinical and prognostic significance

Translating genetic findings to epigenetics: identifying the mechanisms associated with aging after high-radiation exposure on earth and in space

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