Analysis of the Gene Expression of Sparc and Its Prognostic Value for Bladder Cancer

Yamanaka, Manabu D.; Kanda, Kazuya; Li, Ning-chen; Fukumori, Tomoharu; Oka, Nariko; Kanayama, Hiro‐omi; Kagawa, Shunsuke

doi:10.1016/s0022-5347(05)65623-6

Cited by 90 publications

(67 citation statements)

References 14 publications

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“…9 SPARC has been reported to enhance the invasive capacity of prostate and breast cancer cells, glioma cells, esophageal, bladder and metastatic hepatocellular cancers, invasive meningiomas and malignant melanomas. [24][25][26][27][28][29][30][31][32] In this study, we demonstrated that expression of SPARC is downregulated in colorectal carcinomas. Similar suppression of SPARC has been reported in lung cancer and pancreatic cancer.…”

Section: Discussionmentioning

confidence: 94%

Frequent inactivation of SPARC by promoter hypermethylation in colon cancers

Yang

Kang

Koh

et al. 2007

Intl Journal of Cancer

117

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Epigenetic modification of gene expression plays an important role in the development of human cancers. The inactivation of SPARC through CpG island methylation was studied in colon cancers using oligonucleotide microarray analysis and methylation specific PCR (MSP). Gene expression of 7 colon cancer cell lines was evaluated before and after treatment with the demethylating agent 5-aza-2 0 -deoxycytidine (5Aza-dC) by oligonucleotide microarray analysis. Expression of SPARC was further examined in colon cancer cell lines and primary colorectal cancers, and the methylation status of the SPARC promoter was determined by MSP. SPARC expression was undetectable in 5 of 7 (71%) colorectal cancer cell lines. Induction of SPARC was demonstrated after treatment with the demethylating agent 5Aza-dC in 5 of the 7 cell lines. We examined the methylation status of the CpG island of SPARC in 7 colon cancer cell lines and in 20 test set of colon cancer tissues. MSP demonstrated hypermethylation of the CpG island of SPARC in 6 of 7 cell lines and in all 20 primary colon cancers, when compared with only 3 of 20 normal colon mucosa. Immunohistochemical analysis showed that SPARC expression was downregulated or absent in 17 of 20 colon cancers. A survival analysis of 292 validation set of colorectal carcinoma patients revealed a poorer prognosis for patients lacking SPARC expression than for patients with normal SPARC expression (56.79% vs. 75.83% 5-year survival rate, p 5 0.0014). The results indicate that epigenetic gene silencing of SPARC is frequent in colon cancers, and that inactivation of SPARC is related to rapid progression of colon cancers. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 94%

Frequent inactivation of SPARC by promoter hypermethylation in colon cancers

Yang

Kang

Koh

et al. 2007

Intl Journal of Cancer

117

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show abstract

“…In addition to its physiological role, SPARC has been linked to cancer progression as many cancer types present increased levels of SPARC expression upon invasion or metastasis (Rempel et al, 1998;Loging et al, 2000;Bradshaw and Sage, 2001;Framson and Sage, 2004). SPARC is highly expressed in a wide range of human malignant neoplasms, and the deregulated expression of SPARC is often correlated with disease progression and/or poor prognosis (Bellahcene and Castronovo, 1995;Porte et al, 1995Porte et al, , 1998Porter et al, 1995;Massi et al, 1999;Yamanaka et al, 2001). It can interact with different ECM proteins like collagens, matrix metalloproteinases and growth factors modulating the cell shape, growth, adhesion and migration.…”

Section: Introductionmentioning

confidence: 99%

TP53INP1 decreases pancreatic cancer cell migration by regulating SPARC expression

et al. 2011

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Tumor protein 53 induced nuclear protein 1 (TP53INP1) is a p53 target gene that induces cell growth arrest and apoptosis by modulating p53 transcriptional activity. TP53INP1 interacts physically with p53 and is a major player in the p53-driven oxidative stress response. Previously, we demonstrated that TP53INP1 is downregulated in an early stage of pancreatic cancerogenesis and when restored is able to suppress pancreatic tumor development. TP53INP1 downregulation in pancreas is associated with an oncogenic microRNA miR-155. In the present work, we studied the effects of TP53INP1 on cell migration. We found that TP53INP1 inactivation correlates with increased cell migration both in vivo and in vitro. The impact of TP53INP1 expression on cell migration was studied in different cellular contexts: mouse embryonic fibroblast and different pancreatic cancer cell lines. Its expression decreases cell migration by the transcriptional downregulation of secreted protein acidic and rich in cysteine (SPARC). SPARC is a matrix cellular protein, which governs diverse cellular functions and has a pivotal role in regulating cell-matrix interactions, cellular proliferation and migration. SPARC was also showed to be upregulated in normal pancreas and in pancreatic intraepithelial neoplasia lesions in a pancreatic adenocarcinoma mouse model only in the TP53INP1-deficient animals. This novel TP53INP1 activity on the regulation of SPARC expression could explain in part its tumor suppressor function in pancreatic adenocarcinoma by modulating cellular spreading during the metastatic process.

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“…5,6 Elevated SPARC expression is associated with disease progression and poor prognosis in melanoma, breast cancer, glioma, bladder cancer and non-small cell lung cancer. [7][8][9][10][11][12] In colorectal cancer (CRC), the role of SPARC is not well understood. 13,14 SPARC is expressed not only by cancer cells but also by stromal cells surrounding the tumor.…”

Section: Introductionmentioning

confidence: 99%

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

Yoshimura

Nagahara²,

Kuo³

et al. 2011

Epigenetics

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Analysis of the Gene Expression of Sparc and Its Prognostic Value for Bladder Cancer

Abstract: A significant correlation was detected of the gene expression level of SPARC with histological grade, pathological stage and bladder cancer prognosis. SPARC may have an important role in bladder cancer progression and provide some additional information in patients with bladder cancer.

Cited by 90 publications

References 14 publications

Frequent inactivation of SPARC by promoter hypermethylation in colon cancers

Frequent inactivation of SPARC by promoter hypermethylation in colon cancers

TP53INP1 decreases pancreatic cancer cell migration by regulating SPARC expression

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

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