Expression of LL-37/hCAP-18 gene in human leukemia cells

Yang, Ying; Zheng, Guoguang; Li, Ge; Zhang, Bin; Song, Yu; Wu, Ke

doi:10.1016/s0145-2126(03)00020-1

Cited by 26 publications

(15 citation statements)

References 8 publications

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“…The context-dependent function of LL-37 poses some difficulties to define and understand its exact role in tumorigenesis. For example, while LL-37 has been shown to promote the growth of ovarian (7), lung (8), and breast cancers (9), the same peptide exerts tumor-suppressing effects in gastric cancer (6), acute myeloid (13), and lymphocytic leukemia (11). Consistent with its role as a tumor suppressor, LL-37 expression is downregulated in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of LL-37 is dysregulated in gastric, ovarian, lung, and breast cancers as well as melanoma and leukemia (6–11). The role of cathelicidin in tumorigenesis is complex and believed to be context-dependent (12).…”

Section: Introductionmentioning

confidence: 99%

“…The role of cathelicidin in tumorigenesis is complex and believed to be context-dependent (12). Acting as a tumor-suppressor, the expression of hCAP18/LL-37 is downregulated in gastric adenocarcinomas and acute myeloid and lymphocytic leukemia (6, 11, 13). In this regard, LL-37 induces cell-cycle arrest and apoptosis in gastric cancer cells and T lymphocytes, respectively (6, 14).…”

Section: Introductionmentioning

confidence: 99%

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Host Immune Defense Peptide LL-37 Activates Caspase-Independent Apoptosis and Suppresses Colon Cancer

et al. 2012

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Cathelicidins are a family of bacteriocidal polypeptides secreted by macrophages and polymorphonuclear leukocytes (PMN). LL-37, the only human cathelicidin, has been implicated in tumorigenesis, but there has been limited investigation of its expression and function in cancer. Here, we report that LL-37 activates a p53-mediated, caspase-independent apoptotic cascade that contributes to suppression of colon cancer. LL-37 was expressed strongly in normal colon mucosa but downregulated in colon cancer tissues, where in both settings its expression correlated with terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling-positive apoptotic cells. Exposure of colon cancer cells to LL-37 induced phosphatidylserine externalization and DNA fragmentation in a manner independent of caspase activation. Apoptogenic function was mediated by nuclear translocation of the proapoptotic factors, apoptosis-inducing factor (AIF) and endonuclease G (EndoG), through p53-dependent upregulation of Bax and Bak and downregulation of Bcl-2 via a pertussis toxin–sensitive G-protein–coupled receptor (GPCR) pathway. Correspondingly, colonic mucosa of cathelicidin-deficient mice exhibited reduced expression of p53, Bax, and Bak and increased expression of Bcl-2 together with a lower basal level of apoptosis. Cathelicidin-deficient mice exhibited an increased susceptibility to azoxymethane-induced colon tumorigenesis, establishing pathophysiologic relevance in colon cancer. Collectively, our findings show that LL-37 activates a GPCR-p53-Bax/Bak/Bcl-2 signaling cascade that triggers AIF/EndoG–mediated apoptosis in colon cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Host Immune Defense Peptide LL-37 Activates Caspase-Independent Apoptosis and Suppresses Colon Cancer

et al. 2012

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“…In addition to the direct effects of cathelicidin on tumor epithelium, cathelicidin may promote tumor growth through alternative mechanisms [36] and is overexpressed in breast cancer [37],[38], lung cancer [39], prostate cancer [40], and ovarian cancer [41]. In contrast, cathelicidin exhibits tumor-suppressing effects in gastric cancer [42], acute myeloid [43], and lymphocytic leukemia [44]. A recent study has further shown that cathelicidin may induce apoptosis through an alternative caspase-independent pathway in colon cancer, suggesting a tumor-suppressing mechanism for cathelicidin in colon tumorigenesis [27].…”

Section: Resultsmentioning

confidence: 99%

Prioritization of Cancer Marker Candidates Based on the Immunohistochemistry Staining Images Deposited in the Human Protein Atlas

Chiang

Han

et al. 2013

PLoS ONE

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Cancer marker discovery is an emerging topic in high-throughput quantitative proteomics. However, the omics technology usually generates a long list of marker candidates that requires a labor-intensive filtering process in order to screen for potentially useful markers. Specifically, various parameters, such as the level of overexpression of the marker in the cancer type of interest, which is related to sensitivity, and the specificity of the marker among cancer groups, are the most critical considerations. Protein expression profiling on the basis of immunohistochemistry (IHC) staining images is a technique commonly used during such filtering procedures. To systematically investigate the protein expression in different cancer versus normal tissues and cell types, the Human Protein Atlas is a most comprehensive resource because it includes millions of high-resolution IHC images with expert-curated annotations. To facilitate the filtering of potential biomarker candidates from large-scale omics datasets, in this study we have proposed a scoring approach for quantifying IHC annotation of paired cancerous/normal tissues and cancerous/normal cell types. We have comprehensively calculated the scores of all the 17219 tested antibodies deposited in the Human Protein Atlas based on their accumulated IHC images and obtained 457110 scores covering 20 different types of cancers. Statistical tests demonstrate the ability of the proposed scoring approach to prioritize cancer-specific proteins. Top 100 potential marker candidates were prioritized for the 20 cancer types with statistical significance. In addition, a model study was carried out of 1482 membrane proteins identified from a quantitative comparison of paired cancerous and adjacent normal tissues from patients with colorectal cancer (CRC). The proposed scoring approach demonstrated successful prioritization and identified four CRC markers, including two of the most widely used, namely CEACAM5 and CEACAM6. These results demonstrate the potential of this scoring approach in terms of cancer marker discovery and development. All the calculated scores are available at http://bal.ym.edu.tw/hpa/.

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“…4c, 5c). This indicates that zebrafish CXC-64 chemokine promoter regulation by transcription factors might not be under the control of lymphoma cell transcription factors, although RAW264.7 cells can express antimicrobial peptides of LL-37/hCAP-18, and protein products may induce chemokine expressions after LPS treatment (Yang et al 2003). One possible explanation of these results is that the zebrafish CXC-64 chemokine may be selectively produced in the zebrafish liver but not lymphoma cells, suggesting that regulation of gene expression by zebrafish CXC-64 chemokine differs across cell lines.…”

Section: Discussionmentioning

confidence: 98%

Organization and promoter analysis of the zebrafish (Danio rerio) chemokine gene (CXC-64) promoter

Chen

Shiau

et al. 2010

Fish Physiol Biochem

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Zebrafish CXC-64, a chemokine representing a superfamily of chemotactic cytokines present in fish, is involved in recruitment, activation, and response to inflammatory stimulation. We cloned and sequenced the genomic DNA of the zebrafish CXC-64 chemokine; it was most similar to CXCL11 from humans and CXCL10 from a catfish. The zebrafish CXC-64 gene is approximately 4.0 kb long and has a four-exon, three-intron structure common to the human CXCL11 gene. However, the promoter region includes a typical TATA box and multi-transcription factor-binding sequences. To understand the roles of lipopolysaccharide (LPS), poly I:poly C, and tumor necrosis factor (TNF)-alpha in regulating zebrafish CXC-64 expression, serial deletions were made in the promoter region of this clone. Different fragments of the zebrafish CXC-64 5'-flanking region were transfected into RAW264.7 (mouse macrophage; Abelson murine leukemia virus transformed) and zfl (zebrafish liver) cells and then treated with 0, 10, 50, 100, and 200 ng/ml LPS, poly I:poly C, or TNF-alpha. The results showed that the promoter activity presented dose-dependent effects in LPS-treated RAW264.7 cells, TNF-alpha-treated RAW264.7 cells, and LPS-treated zfl cells. These results reveal that the zebrafish CXC-64 chemokine gene promoter region can be induced by LPS in both human and fish cell lines, which suggests that it plays an important role in regulating LPS.

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Expression of LL-37/hCAP-18 gene in human leukemia cells

Cited by 26 publications

References 8 publications

Host Immune Defense Peptide LL-37 Activates Caspase-Independent Apoptosis and Suppresses Colon Cancer

Host Immune Defense Peptide LL-37 Activates Caspase-Independent Apoptosis and Suppresses Colon Cancer

Prioritization of Cancer Marker Candidates Based on the Immunohistochemistry Staining Images Deposited in the Human Protein Atlas

Organization and promoter analysis of the zebrafish (Danio rerio) chemokine gene (CXC-64) promoter

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