Differential expression of S100A2 and S100A4 in lung adenocarcinomas: Clinicopathological significance, relationship to p53 and identification of their target genes

Matsubara, Daisuke; Niki, Toshiro; Ishikawa, Shumpei; Goto, Akiteru; Ohara, Etsuko; Yokomizo, Takehiko; Heizmann, Claus W.; Aburatani, Hiroyuki; Moriyama, Sachiko; Moriyama, Hirokazu; Nishimura, Yoshihiro; Funata, Nobuaki; Fukayama, Masashi

doi:10.1111/j.1349-7006.2005.00121.x

Cited by 69 publications

(60 citation statements)

References 46 publications

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“…This may indicate that the S100A2 gene acts differently in ADC than in SCC tumourigenesis, and that the pathways including S100A2 are different in different NSCLC types. It has been published that the S100A2 gene is down-regulated in lung ADC cell lines, but frequently observed in primary lung ADC cells [50], so there is more proof that the expression of S100A2 is precisely regulated with different mechanisms, and it may be that the deregulation of this gene's expression is specific to the pathological characteristics of different tumours. The study is limited by the numbers of specimens included in the study and by its retrospective nature.…”

Section: Discussionmentioning

confidence: 99%

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Stražišar

Mlakar

Glavač

2009

Cellular and Molecular Biology Letters

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Abbreviations used: ADC -adenocarcinoma; CDK2 -cyclin-dependent kinase 2; cDNAcomplementary DNA; COX-2 -cyclooxygenase 2; C T -cycle threshold; DNAdeoxyribonucleic acid; GAPDH -glyceraldehyde-3-phosphate dehydrogenase; hTERThuman telomerase reverse transcriptase; IHC -immunohistochemistry; LATS2 -homolog of large tumour suppressor 2, Drosophilae; LCC -large cell carcinoma; MDM2 -mouse double minute 2 homolog; mRNA -messenger RNA; NSCLC -non-small cell lung cancer; p21 -cyclin-dependent kinase inhibitor 1A; p53 -tumour protein p53; PCR -polymerase chain reaction; pTNM -pathological tumour-node-metastasis; RB -retinoblastoma; RNAribonucleic acid; r s -Spearman's rank correlation coefficient; RT-PCR -real time PCR; S100A2 -S100 calcium binding protein A2; SCC -squamous cell carcinoma , we analysed the expression of the COX-2, hTERT, MDM2, LATS2 and S100A2 genes and researched the relationships between the NSCLC types and the differences in expression levels. The differences in the expression levels of the LATS2, S100A2 and hTERT genes in different types of NSCLC are significant. hTERT and COX-2 were over-expressed and LATS2 under-expressed in all NSCLC. We also detected significant relative differences in the expression of LATS2 and MDM2, hTERT and MDM2 in different types of NSCLC. There was a significant difference in the average expression levels in S100A2 for ADC and SCC. Our study shows differences in the expression patterns within the NSCLC group, which may mimic the expression of the individual NSCLC type, and also new relationships in the expression levels for different NSCLC types.

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Section: Discussionmentioning

confidence: 99%

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Stražišar

Mlakar

Glavač

2009

Cellular and Molecular Biology Letters

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“…The histological criteria for vascular, lymphatic, and pleural invasion were as described earlier. 13,14 Stromal invasion was evaluated according to the criteria described by Terasaki et al 8 …”

Section: Patients and Tumorsmentioning

confidence: 99%

Subepithelial myofibroblast in lung adenocarcinoma: a histological indicator of excellent prognosis

et al. 2009

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We report here the presence of subepithelial myofibroblasts in pure bronchioloalveolar carcinoma and a subset of invasive lung adenocarcinoma. The subepithelial myofibroblasts we describe were observed in a peculiar location beneath the cancer cells in the alveolar septa. Immunohistochemically, they were positive for a-smooth muscle actin and calponin, but negative for desmin and h-caldesmon. To gain insight into their biological significance, we examined 116 surgically resected lung adenocarcinomas. The resected tumors included 13 bronchioloalveolar carcinomas, 20 mixed type adenocarcinomas with bronchioloalveolar carcinoma components, 57 papillary adenocarcinomas, 22 solid adenocarcinomas with mucin, and 4 acinar adenocarcinomas. All specimens were immunostained for a-smooth muscle actin to visualize the myofibroblasts. In all of the pure bronchioloalveolar carcinomas observed, the subepithelial myofibroblasts were completely preserved adjacent to the cancer cells. In mixed adenocarcinomas with bronchioloalveolar carcinoma components, subepithelial myofibroblasts were present in the bronchioloalveolar carcinoma components, but scanty in the invasive areas, where stromal myofibroblasts emerged between the cancer cell nests. Subepithelial myofibroblasts were retained, however, in the invasive areas of a subset of invasive adenocarcinomas. Survival analysis showed that the retention of subepithelial myofibroblasts in these invasive tumors was associated with low rates of lymphatic and vascular invasion, a low rate of lymph node involvement, and an excellent patient survival. These results suggest that subepithelial myofibroblasts increase in bronchioloalveolar carcinomas, but are gradually replaced by typical stromal myofibroblasts during progression into invasive cancer. A subset of invasive adenocarcinomas retains subepithelial myofibroblasts. Analysis of subepithelial myofibroblasts may be helpful in identifying a subset of lung adenocarcinoma with excellent prognosis.

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“…Primers for MMP-11 were designed using Primer3 software, while those specific for MMP-9, S100A2, and Clusterin were previously described. [17][18][19] The sequences for the primers are the following: S100A2: 5′-CTGGCTGTGCTGGTCACTAC-3′ (forward); 5′-TGGGCAGCTCCTTGTGCAGA-3′ (reverse); MMP-9: 5′-GCACGACGTCTTCCAGTACC-3′ (forward), 5′-CAG GATGTCATAGGTCACGTAGC-3′ (reverse); MMP-11: 5′-CTCGTGGGTCCTGACTTCTT-3′ (forward), 5′-GCAG TTGTCATGGTGGTTGT-3′ (reverse); Clusterin: 5′-GAG CAGCTGAACGAGCAGTTT-3′ (forward), 5′-CTTCGCC TTGCGTGAGGT-3′ (reverse); β-Actin: 5′-CCCAGCACA ATGAAGATCAA-3′ (forward), 5′-CGATCCACACGGA GTACTTG-3′ (reverse).…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

Altered gene expression in conjunctival squamous cell carcinoma

et al. 2016

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Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

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Differential expression of S100A2 and S100A4 in lung adenocarcinomas: Clinicopathological significance, relationship to p53 and identification of their target genes

Cited by 69 publications

References 46 publications

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Subepithelial myofibroblast in lung adenocarcinoma: a histological indicator of excellent prognosis

Altered gene expression in conjunctival squamous cell carcinoma

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