Down regulation of 3p genes, <i>LTF, SLC38A3</i> and <i>DRR1</i>, upon growth of human chromosome 3–mouse fibrosarcoma hybrids in severe combined immunodeficiency mice

Kholodnyuk, Irina; Kozireva, Svetlana; Kost‐Alimova, Maria; Kashuba, Vladimir I.; Klein, George; Imreh, Stefan

doi:10.1002/ijc.21794

Cited by 49 publications

(42 citation statements)

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“…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: 67%

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

Luo

Zhou

et al. 2015

Oncology Letters

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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.

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Section: Discussionsupporting

confidence: 67%

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

Luo

Zhou

et al. 2015

Oncology Letters

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“…Accordingly TU3A is characterized as a candidate of tumor suppressor gene (TSG) because of its typical expression pattern as a TSG and the fact that introduction of TU3A suppresses tumor cell proliferation and induces apoptosis (2,6,17,18). Similar to TU3A, as a member of FAM107, HITS was shown to be decreased or absent in gastric and colorectal cancers and to inhibit tumor cell proliferative responses to growth factors in the present study.…”

Section: Discussionmentioning

confidence: 60%

Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation

Nakajima¹

2010

Int J Oncol

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Abstract. The Family with sequence similarity 107 (FAM107) possesses an N-terminal domain of unknown function (DUF1151) that is highly conserved beyond species. In human, FAM107A termed TU3A/DRR1 has been reported as a candidate tumor suppressor gene which expression is downregulated in several types of cancer, however no studies have investigated the other family protein, FAM107B. In the present study, we designated FAM107B as heat shockinducible tumor small protein (HITS) and studied its expression and functional properties in cancer. HITS is an 18-kDa nuclear protein expressed in a variety of tissues including stomach, colon, lung and lymphoid organs. In human gastric and colorectal cancers and a mouse model of colon cancer, its expression in tumor cells was much lower than normal epithelial cells, while expression pattern and intensity varied among different histological types of cancer. In functional analysis in vitro, forced expression of this protein suppresses the cellular responses to growth factors. Furthermore, HITS gene carries the promoter region providing heat shock transcription factor (HSF) binding sites and amplifying the transcription of HITS by heat shock or hyperthermia treatment both in vitro and in vivo. Thus HITS would be a potential tumor suppressor gene similar to TU3A containing heat responding elements, which contrasts with previously described oncogenic activities of other heat shock proteins such as HSP70 and HSP90.

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“…The deletion in chromosomal 3p21.31 was also reported in different cancers including HNSCC. [28][29][30] Deletions in the D1 and D3 regions overlapped with the deletions in C3CER1 (Common Eliminated Region 1) and 21.3 LUCA (Lung Cancer) reported by Kost-Alimova and Imreh 30 and Senchenko et al, 31 respectively. However, deletion in the D2 region has not been reported earlier.…”

Section: Resultsmentioning

confidence: 75%

Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis

Ghosh

Maiti

et al. 2008

Intl Journal of Cancer

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The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 squamous cell carcinoma of head and neck, both deletion and promoter methylation have been seen in these genes except for CDC25A and SCOTIN where no methylation has been detected. The alteration of LIMD1 was highest (50%) in the mild dysplastic lesions and did not change significantly during progression of tumor indicating its association with this stage of the disease. It was evident that alterations of LTF, CDC25A and CACNA2D2 were associated with development of moderate dysplastic lesions, while alterations in RASSF1A and CACNA2D2 were needed for progression. Novel somatic mutations were seen in exon 1 of LIMD1 (7%), intron 3/exon4 splice junction of LTF (2%) and exon 7 of cdc25A (10%). Quantitative RT-PCR analysis revealed mean reduced expression of the genes in the following order: LTF (67.6 6 16.8) > LIMD1 (53.2 6 20.1) > CACNA2D2 (23.7 6 7.1) > RASSF1A (15.1 6 5.6) > CDC25A (5.3 6 2.3) > SCOTIN (0.58 6 0.54). Immunohistochemical analysis of CDC25A showed its localization both in cytoplasm and nucleus in primary lesions and oral cancer cell lines. In absence of HPV infection, LTF and RASSF1A alterations jointly have adverse impact on survival of tobacco addicted patients. Thus, our data suggested that multiple candidate TSGs in the chromosomal 3p21.31 region were differentially associated with the early dysplastic lesions of head and neck. ' 2008 Wiley-Liss, Inc.Key words: dysplastic lesions; expression; head and neck squamous cell carcinoma; mutation; 3p21.31; survival study; tumor suppressor genes; methylation Head and neck squamous cell carcinoma of (HNSCC) is the sixth most common cancer worldwide and it accounts for 30-40% of all cancer types in Indian subcontinent.1 HNSCC is a heterogeneous epithelial malignant disease arising from mucosa of the upper aerodigestive tract (oral cavity, larynx, oropharynx and hypopharynx) with complex molecular abnormalities. Although the major and common environmental carcinogenic risk factors of tobacco, alcohol, betel quid and HPV infection have long been recognized, details of the genetic and epigenetic events leading to the development and spread of HNSCC remain largely unknown. Array-based gene expression profiling focused the transition of normal mucosa to premalignant lesion as the most important event with majority of transcriptional alterations rather than transition from premalignant lesion to invasive carcinoma during the progression of HNSCC.2 In microcell hybrid system, it has been shown that the introduction of chromosome 3 can suppress the tumorigenicity of oral cancer cell lines, suggesting the presence of at least 1 tumor suppressor gene (TSG) in this chromosome associated with the development of HNSCC.3 According to a recent tumor progr...

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Down regulation of 3p genes, LTF, SLC38A3 and DRR1, upon growth of human chromosome 3–mouse fibrosarcoma hybrids in severe combined immunodeficiency mice

Cited by 49 publications

References 48 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

Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation

Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis

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