Role of PTEN and MMP‐7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma

Zheng, Haixue; Sun, Jian; Li, Xiaohan; Yang, Xinyi; Zhang, Yin‐Chang; Xin, Yan

doi:10.1046/j.1440-1827.2003.01542.x

Cited by 176 publications

(208 citation statements)

References 36 publications

(39 reference statements)

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“…Altered DNA copy number status or expression of several genes, such as CD44, p27 kip1 , Bax, VEGF, nm23, TNFRSF6B and several matrix metalloproteinases (MMPs), is associated with lymph node metastasis in gastric cancer [7][8][9][10][11][12][13][14][15][16][17]. In addition, genomewide mRNA expression analyses have been performed in order to determine genetic signatures correlated with lymph node status in gastric cancer patients [18,19].…”

Section: Introductionmentioning

confidence: 99%

Losses of Chromosome 5q and 14q Are Associated with Favorable Clinical Outcome of Patients with Gastric Cancer

et al. 2012

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Purpose. To improve the clinical outcome of patients with gastric cancer, intensified combination strategies are currently in clinical development, including combinations of more extensive surgery, (neo)adjuvant chemotherapy, and radiotherapy. The present study used DNA copy number profiling to identify subgroups of patients with different clinical outcomes. We hypothesize that, by identification of subgroups, individual treatment strategies can be selected to improve clinical outcome and to reduce unnecessary treatment toxicity for patients with gastric cancer.Experimental Design. DNA from 206 gastric cancer patients was isolated and analyzed by genomewide array comparative genomic hybridization. DNA copy number profiles were correlated with lymph node status and patient survival. In addition, heat shock protein 90 (HSP90) expression was analyzed and correlated with survival in 230 gastric cancer patients.Results. Frequent (>20%) DNA copy number gains and losses were observed on several chromosomal regions. Losses on 5q11.2-q31.3 and 14q32.11-q32.33 (14% of patients) were correlated with good clinical outcome in univariate and multivariate analyses, with a median diseasefree survival interval of 9.2 years. In addition, loss of expression of HSP90, located on chromosome 14q32.2, was correlated with better patient survival. Conclusion. Genomewide DNA copy number profiling allowed the identification of a subgroup of gastric cancer patients, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 or low HSP90 protein expression, with an excellent clinical outcome after surgery alone. We hypothesize that this subgroup of patients most likely will not benefit from (neo)adjuvant systemic treatment and/or radiotherapy, whereas anti-HSP90 therapy may have clinical potential in patients with HSP90-expressing gastric cancer, pending validation in an independent dataset. The Oncologist 2012;17:653-662

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Section: Introductionmentioning

confidence: 99%

Losses of Chromosome 5q and 14q Are Associated with Favorable Clinical Outcome of Patients with Gastric Cancer

et al. 2012

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“…MMP-2 and MMP-9 secretion is elevated in several types of human cancers and their elevated expression has been associated with the poor prognosis of cancer patients (19)(20)(21). The present study employed a firefly luciferase-based reporter assay to analyze the interaction of Osterix with the MMP2 and MMP9 promoters.…”

Section: Discussionmentioning

confidence: 99%

Osterix transcriptional factor is involved in the metastasis of human breast cancers

Dai

Zhou

et al. 2015

Oncology Letters

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Abstract. The transcriptional factor Osterix is specifically expressed in bone tissues to regulate the differentiation and maturation of osteoblasts. Recent studies have also identified the expression of Osterix in a number of cancer tissues, such as kidney and lung cancers. However, the association of Osterix with the metastasis of breast cancers has never been reported. The present study, for the first time, provides evidence supporting the involvement of Osterix in breast cancer metastasis. Western blotting was employed to investigate the expression of Osterix in a number of human breast cancer cell lines with different metastatic features. Gain-of-function and loss-of-function experiments were performed in MCF7 cells (low level of metastasis) and MDA-MB-361 cells (high level of metastasis). The expression of several metastasis-associated genes was analyzed by western blotting and quantitative polymerase chain reaction. A firefly luciferase-based reporter gene assay was conducted in order to study whether Osterix regulated the promoter activities of the MMP2 and MMP9 genes, which play critical roles in cancer metastasis. The results showed that Osterix was highly expressed in the MDA-MB-231 and MDA-MB-361 cells, but was not detectable in the MCF7 cells. The overexpression of Osterix in the MCF7 cells promoted the expression of VEGF, MMP9 and β-catenin, while downregulating the expression of E-cadherin. In addition, suppression of Osterix expression in the MDA-MB-361 cells reversed the alteration of VEGF, MMP9, β-catenin and E-cadherin expression. A reporter gene assay suggested that Osterix activated MMP2 and MMP9 promoter activity. In conclusion, Osterix is involved in the metastasis of human breast cancer and may be a target for the efficient treatment of human breast cancers.

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“…Gelatinase A (MMP-2) and gelatinase B (MMP-9) have the potency to carry out angiogenic activities [154]. Their release from the endothelial cells is promoted by FGFs [155,156]. Angiogenesis requires the migration of ECs to form the new vessels.…”

Section: Fgfs and Fgfrs: Roles In Angiogenesismentioning

confidence: 99%

Fibroblast Growth Factors and their Emerging Cancer-Related Aspects

Khalid¹,

Javaid²

2016

J Cancer Sci Ther

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Role of PTEN and MMP‐7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma

Cited by 176 publications

References 36 publications

Losses of Chromosome 5q and 14q Are Associated with Favorable Clinical Outcome of Patients with Gastric Cancer

Losses of Chromosome 5q and 14q Are Associated with Favorable Clinical Outcome of Patients with Gastric Cancer

Osterix transcriptional factor is involved in the metastasis of human breast cancers

Fibroblast Growth Factors and their Emerging Cancer-Related Aspects

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