Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma

Tsubaki, Masanobu; Yamazoe, Yuzuru; Yanae, Masashi; Satou, Takao; Itoh, Tatsuki; Kaneko, Junichi; Kidera, Yasuhiro; Moriyama, Kenzo; Nishida, Shozo

doi:10.1016/j.cyto.2011.01.005

Cited by 69 publications

(47 citation statements)

References 29 publications

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“…It is involved in mediating survival signals that rescue Ewing tumor from fibroblast growth factor 2-induced cell death (20). Blockade of AKT pathway reduces the expression of TGF-ã s angiogenic factors in mouse osteosarcoma (21).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of AXL Receptor Tyrosine Kinase in Osteosarcoma Cells Leads to Decreased Proliferation and Increased Apoptosis

Zhang

et al. 2013

Int J Immunopathol Pharmacol

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Dysregulation of the Axl receptor tyrosine kinase (RTK) has been implicated in the development and progression of a variety of malignancies. Axl is known to activate strong anti-apoptotic signaling pathways that promote oncogenesis. However, the role of AxI plays in osteosarcoma (OS) remains elusive. The present study aimed to investigate the clinical significance and function of AxI in human OS. Forty cases of OS and corresponding adjacent non-cancerous tissues (ANCT) were collected. The expression of AxI was assessed using immunohistochemical assay through tissue microarray procedure. A loss-of-function experiment was performed to investigate the effects of small hairpin RNA (shRNA)-mediated knockdown of AxI on the expression of p-AKT, poly ADP-ribose polymerase (pARP) and Ki-67, the proliferative activities, indicated by MTT assay, and the apoptotic index in OS MG-63 cells. As a result, the expression of AxI was found in OS tissues with higher strong reactivity rate, compared with the ANCT (75.0% vs 20.0%, P=O.OOO), but it did not associate with the age, gender, tumor size, TNM staging and distant metastases (each P>0.05). Furthermore, knockdown of AxI inhibited the proliferative activities and induced apoptosis in MG-63 cells with decreased expression of p-AKT, and Ki-67 and increased expression of PARP. In conclusion, our findings suggest that Axl is highly expressed in most of the OS tissues compared with the ANCT, and knockdown of AxI inhibits proliferation and induces apoptosis of OS cells possibly through down regulation of the AKT pathway, suggesting that our findings may provide new insights into the potential therapeutic target for cancer.Osteosarcoma (OS) is a malignant bone tumor that typically occurs in children, adolescents and young adults. Incorporation of chemotherapy into initial treatment significantly increases the cure rate. However, about 40% of patients still die from lung metastases (1). It is very important to develop biomarkers that can inform therapy and provide prognostic insight, especially into identifying poor prognosis patients who should be offered more aggressive therapy at an early time point in the clinical continuum (2, 3). Tumor is also a genetic disease developing from a multi-step process. Single or multiple mutations in genes related to growth control, invasion and metastasis form the molecular genetic basis of malignant transformation and tumor progression (4). Therefore, identification of key genes and targets related to cancer is crucial for prevention and treatment of OS.Axl is a receptor tyrosine kinase (RTK) that was originally cloned from cancer cells. Axl belongs to the TAM (Tyr03, Axl and Mertk) family of receptor tyrosine kinases. Growth-arrest-specific protein 6 (Gas6) is a ligand for Axl, and activation of AxI protects cancer cells from apoptosis and

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Section: Discussionmentioning

confidence: 99%

Knockdown of AXL Receptor Tyrosine Kinase in Osteosarcoma Cells Leads to Decreased Proliferation and Increased Apoptosis

Zhang

et al. 2013

Int J Immunopathol Pharmacol

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“…Angiogenic factor has played important role in tumor angiogenesis. Previous research has revealed that vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-β1 (TGF-β1) have close relevance to a variety of tumor progression (Kim et al, 2009;Tsubaki et al, 2011). In addition, endostatin (ES) is considered to be related with tumor prognosis and microvessel density.…”

Section: Introductionmentioning

confidence: 99%

Clinical Predictive Value of Serum Angiogenic Factor in Patients with Osteosarcoma

Chen

Chen²,

Hou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…In summary, E2 promptly activates the PI3K/Akt signal pathway in Ishikawa cells via ER-dependent and ER-independent mechanisms (Guo et al, 2006). The expression of TGF-β family members is reduced by blockade of the PI3K/Akt signal pathway in mouse osteosarcoma (Tsubaki et al, 2011). Activated Akt leads to upregulation of TGF-β1 in mesangial cells (Wu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

Zong

Jiang

Zhao

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:The lysyl oxidase (LOX) family encodes the copper-dependent amine oxidases that play a key role in determining the tensile strength and structural integrity of connective tissues by catalyzing the crosslinking of elastin or collagen. Estrogen may upregulate the expression of LOX and lysyl oxidase-like 1 (LOXL1) in the vagina. The objective of this study was to determine the effect of estrogen on the expression of all LOX family genes in the urogenital tissues of accelerated ovarian aging mice and human Ishikawa cells. Mice and Ishikawa cells treated with estradiol (E2) showed increased expression of LOX family genes and transforming growth factor β1 (TGF-β1). Ishikawa cells treated with TGF-β1 also showed increased expression of LOX family genes. The Ishikawa cells were then treated with either E2 plus the TGF-β receptor (TGFBR) inhibitor SB431542 or E2 alone. The expression of LOX family genes induced by E2 was reduced in the Ishikawa cells treated with TGFBR inhibitor. Our results showed that E2 increased the expression of the LOX family genes, and suggest that this induction may be mediated by the TGF-β signal pathway. E2 may play a role in regulating the expression of LOX family genes.

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Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma

Cited by 69 publications

References 29 publications

Knockdown of AXL Receptor Tyrosine Kinase in Osteosarcoma Cells Leads to Decreased Proliferation and Increased Apoptosis

Knockdown of AXL Receptor Tyrosine Kinase in Osteosarcoma Cells Leads to Decreased Proliferation and Increased Apoptosis

Clinical Predictive Value of Serum Angiogenic Factor in Patients with Osteosarcoma

Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

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