Lactoferrin Down-Regulates G1 Cyclin-Dependent Kinases during Growth Arrest of Head and Neck Cancer Cells

Yan, Xuemin; Monitto, Constance L.; Minhas, Khalid M.; Sidransky, David

doi:10.1158/1078-0432.ccr-04-0988

Cited by 93 publications

(83 citation statements)

References 28 publications

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“…[39][40][41][42][43][44] We found that LTF treatment inhibited cyclin D1 expression and Rb phosphorylation, and increased levels of p21 and p27 expression. Hence, upregulation of p21 and p27 may downregulate the expression of cyclin D1 and Rb phosphorylation, 45,46 contributing to NPC growth inhibition. Further analysis of MAPK signaling events revealed that LTF treatment for 12 or 24 hr dramatically reduced expression levels of JNK2 and c-Jun in addition to ERK1/ 2 phosporylation or c-fos expression, respectively.…”

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

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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.

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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

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“…Single-dimensional Western blot analysis involved electrophoresis of cell lysates prepared as described, 15 on NuPAGE 4-12% Bis-Tris gels (Invitrogen). Gels were equilibrated in buffer and electroblotted onto nitrocellulose membranes.…”

Section: Western Blottingmentioning

confidence: 99%

“…To independently determine whether these antibodies detected the appropriate target proteins by molecular weight and abundance in highly expressing cells, polyacrylamide gel electrophoresis (PAGE) followed by Western blots was performed 15 (Fig. 4).…”

Section: Immunodetection With Quantum Dot Fluorophores In Cultured Cellsmentioning

confidence: 99%

Quantitation of HER2 and telomerase biomarkers in solid tumors with IgY antibodies and nanocrystal detection

Yan

Gao²,

Gannot

et al. 2008

Intl Journal of Cancer

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In an effort to improve affinity biomarker validation in fixed patient tissue specimens, we have developed a novel quantum dotbased bioimaging system that utilizes chicken IgY antibody for high sensitivity and specificity relative quantitation of cancer proteins. Monospecific, polyclonal IgYs were generated against human HER2 and telomerase, and analytically validated for specificity by western blot and immunohistochemistry on tumor and normal cells and for relative affinity by layered peptide array (LPA). IgYs bound desired targets in cell lines and fixed tissues and showed greater affinity than commercial mammalian antibodies for both HER2 and telomerase proteins. In tissue microarray experiments, HER2 quantitation with IgY antibody and quantum dot imaging correlated well with chromogenic in situ hybridization (CISH), whereas telomerase quantitation suggested a trend toward correlation with prostate cancer Gleason Grade and differentiation. Although patient numbers were small, these findings demonstrate the feasibility of relative quantitation of cancer biomarkers with IgY and quantum dot fluorophores, and show promise for rigorous clinical validation in large patient cohorts. ' 2008 Wiley-Liss, Inc.Key words: IgY antibody; cancer biomarker; HER2; telomerase; quantum dots Few new early cancer biomarkers have surfaced in recent years. 1 Among novel proteomic biomarkers for early cancer detection, some have proven controversial. 2,3 Analytical and clinical validation of cancer biomarkers has suffered from bias in the design, conduct and interpretation of such research, 4 incompletely validated imaging, 5 and lack of affinity standards 6 and antibodies that did not, in fact, detect correct targets. 7 Here, we describe a novel approach to cell-based bioimaging with relative quantitation for biomarker validation. We report characterization of two new IgY antibodies for quantitation of model cancer biomarker systems, HER2 and telomerase, 8 and explore analytical improvements, including low cross-reactivity IgY-isotype chicken polyclonal antibodies raised against recombinant polypeptides; digital quantification of antibody signals with streptavidin-conjugated semiconductor nanocrystals to obviate photobleaching of organic fluorescent dyes; complete z-plane fluorescence image capture using 3D-deconvolution microscopy; high-throughput, automated, robotic slide processing; and quantitative, massively parallel, high-throughput analysis of peptide antigen-antibody interactions by layered peptide array (LPA) technology. 9

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“…Recently, some studies have also suggested antitumor activities for LF [2,6,9,13,14]. In previous studies, LF has been shown to inhibit the growth of some tumor cell lines, including head and neck squamous cell carcinoma (SCCVII, O12), human breast cancer epithelial cells (MCF-7, MDA-MB-231) and murine colon adenocarcinoma cells (colon-26) [2,6,9,13,14].…”

mentioning

confidence: 99%

“…In previous studies, LF has been shown to inhibit the growth of some tumor cell lines, including head and neck squamous cell carcinoma (SCCVII, O12), human breast cancer epithelial cells (MCF-7, MDA-MB-231) and murine colon adenocarcinoma cells (colon-26) [2,6,9,13,14]. Furthermore, phase I trials of talactoferrin alfa, a recombinant human lactoferrin, have been completed using human refractory solid tumors [4].…”

mentioning

confidence: 99%

The Antiproliferative Effect of Bovine Lactoferrin on Canine Mammary Gland Tumor Cells

Yamada

Sato

Kobayashi

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. Lactoferrin has several biological activities, including antitumor activities in some human and animal tumor cells. Clinical trials have been carried out in human medicine based on these effects. However, the antitumor effects of lactoferrin in veterinary medicine remain unknown. In this in vitro study, we demonstrated that co-incubation of canine mammary gland tumor cells (CIPp and CHMp) and bovine lactoferrin induced growth arrest of tumor cells. This growth arrest was associated with induction of G1 arrest. Furthermore, this effect was stronger in tumor cells than in normal cells. These findings demonstrate that bovine lactoferrin has anti-tumor activity in canine mammary tumors and has the potential for use in tumor-bearing dogs. KEY WORDS: bovine lactoferrin, canine mammary gland tumor cell, G1 arrest.

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Lactoferrin Down-Regulates G1 Cyclin-Dependent Kinases during Growth Arrest of Head and Neck Cancer Cells

Cited by 93 publications

References 28 publications

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

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

Quantitation of HER2 and telomerase biomarkers in solid tumors with IgY antibodies and nanocrystal detection

The Antiproliferative Effect of Bovine Lactoferrin on Canine Mammary Gland Tumor Cells

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