Genetic and Epigenetic Alterations of <i>LTF</i> at 3p21.3 in Nasopharyngeal Carcinoma

Yi, Hongmei; Li, Hui; Peng, Dan; Zhang, Hejun; Wang, Lei; Zhao, Ming; Yao, Kai-Tai; Ren, Chao

doi:10.3727/000000006783981008

Cited by 39 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer (24). Previous studies have also indicated that LTF may have a direct effect on tumor cell growth, as suggested by the fact that LTF and an LTF splice variant are downregulated or absent in certain types of cancer (25)(26)(27)(28). The results of the present study indicate that LTF may also serve as an important tumor suppressor gene in GC.…”

Section: Discussionsupporting

confidence: 58%

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

Luo

Zhou

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. In advanced and metastatic GC, conventional chemotherapy results in limited efficacy and the average survival rate is currently approximately 10 months. Dysregulated activation of numerous genes, including zinc finger, DHHC-type containing 14; caspase-associated recruitment domain-containing protein; and Ras association domain family member 10, have been implicated in GC. The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. However, the mechanism of the tumor suppressor function of LTF in GC remains unclear. In the present study, the expression levels of LTF in patient GC tissue samples were investigated using reverse transcription-quantitative polymerase chain reaction, and it was demonstrated that the LTF mRNA expression level in GC tissue samples was reduced by ~20-fold compared with the adjacent non-cancerous tissues (t=4.56, P<0.01). A similar trend in LTF protein expression was observed by western blot analysis. Furthermore, the present study demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway intermediates p38, c-Jun N-terminal kinase (JNK) and c-Jun were highly expressed in GC tissue samples, and indicated that LTF downregulation may be associated with the dysregulation of the MAPK signaling pathway in GC tissues. In addition, the present study indicated that LTF overexpression reduced the expression of p38, JNK2 and c-Jun in the GC cell line, SGC7901. The present study demonstrates that LTF expression is downregulated in GC tissues and that LTF may serve an important role in the dysregulation of the MAPK signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 58%

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

Luo

Zhou

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…9 LTF may act as a tumor suppressor to downregulate the progression and metastasis of NPC. As hypermethylation in the LTF promoter region was observed in a large number of primary NPC tissues, 37 inactivation of LTF gene expression in NPC is likely to be mediated by promoter hypermethylation and histone deacetylation of the tumor suppressor gene. 8,30 Notably, LTF expression was detected in several advanced stage NPCs after metastasis to local lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Lactotransferrin: A candidate tumor suppressor—Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen‐activated protein kinase pathway

Zhou

Zeng

Zhang

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

Lactotransferrin (LTF) has been shown to regulate tumorogenesis. However, little is known about the role of LTF in regulating the development of human nasopharyngeal carcinoma (NPC). The aim of our study was to investigate whether LTF could regulate the development of NPC by characterizing the pattern of LTF expression in human NPC tissues using cDNA and tissue microarrays. Loss of LTF expression was observed in a significantly higher frequency of NPC tissues compared to that in nontumor nasopharyngeal epithelial tissues. While 61.25% of NPC tissues at the T1/T2 stage were positive for LTF expression, only 40.82% of NPC at the T3/T4 stage were stained by anti-LTF. Similarly, 41.58% of NPC with local lymph node metastasis displayed LTF expression, a value significantly lower than the 46.36% in primary tumors (p < 0.05). These findings suggest that LTF may negatively regulate the development and metastasis of NPC in vivo. Furthermore, overexpression of or treatment with LTF inhibited the proliferation of NPC cells and promoted cell cycle arrest at the G 0 /G 1 phase in vitro. While LTF treatment downregulated expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), expression of p21 and p27 in 5-8F NPC cells was enhanced. Moreover, LTF treatment modulated the mitogen-activated protein kinase (MAPK) pathway, but did not affect p53 and STAT3 expression in 5-8F NPC cells. Thus LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway. Therefore, our findings provide new insights in understanding the mechanism(s) underlying the action of LTF in regulating the development of human NPC.

show abstract

“…Nair et al [33] found that SEMA3B expression in neuroblastoma cells increased significantly after treatment with another de-methylation agent, 5-aza-2-deoxycytidylate. However, Yi et al [34] found that 100% of nasopharyngeal carcinoma samples and 73.3% of chronic nasopharyngitis tissue tested showed hypermethylation of the SEMA3B promoter, which suggests that hypermethylation of the SEMA3B promoter is related to inflammation, aging or other physiological and pathological conditions; that are un elated to the pathogenesis and development of nasopharyngeal carcinoma. Studies by Nair et al [33] also indicated that cells without methylation of the SEMA3B promoter have low expression levels of SEMA3B, suggesting that methylation is not necessary for the inactivation of SEMA3B.…”

Section: Inactivation Of Sema3b Tumor Suppression and The Relationshimentioning

confidence: 99%

“…Riquelme et al [35] [34] reported that the total LOH frequency of SEMA3B in patients with nasopharyngeal carcinomas was 45%, and the expression level of the SEMA3B gene was negatively correlated with LOH. However, Osada et al [36] did not find a correlation between LOH and mRNA expression deficiency of SEMA3B in ovarian epithelial samples.…”

Section: Inactivation Of Sema3b Tumor Suppression and The Relationshimentioning

confidence: 99%

Semaphorin 3B Gene Suppresses Tumor Growth Through the p53 Signaling Pathway and Neuropilin Receptors

Ma¹

2017

AJCEM

View full text Add to dashboard Cite

Abstract:The semaphorin family has been demonstrated to possess tumor suppressor activity; semaphorin 3B (SEMA3B) is differentially expressed in several types of tumors, and has been identified as a tumor suppressor gene. SEMA3B is shown to be a target gene of p53, and it suppresses tumor growth through the p53 signaling pathway. The mechanisms underlying tumor suppression by SEMA3B include neuropilin receptors (NRP1 and NRP2), which reduce the action of vascular endothelial growth factor (VEGF), thus, inhibiting tumor angiogenesis. Deficiency or down-regulation of SEMA3B expression can be found in a variety of malignant tumors including lung cancer, ovarian cancer, nervous system tumors, and hepatobiliary tumors, and this suppression involves methylation, loss of heterozygosity (LOH) and enzyme cleavage. This review summarizes recent research approaches on the tumor suppression effects and mechanisms of SEMA3B.

show abstract

Genetic and Epigenetic Alterations of LTF at 3p21.3 in Nasopharyngeal Carcinoma

Cited by 39 publications

References 0 publications

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

Lactotransferrin: A candidate tumor suppressor—Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen‐activated protein kinase pathway

Semaphorin 3B Gene Suppresses Tumor Growth Through the p53 Signaling Pathway and Neuropilin Receptors

Contact Info

Product

Resources

About