Growth Inhibitory Effects of Flavonoids in Human Thyroid Cancer Cell Lines

Yin, Fen; Giuliano, Armando E.; Herle, André J. Van

doi:10.1089/thy.1999.9.369

Cited by 105 publications

(82 citation statements)

References 31 publications

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“…6 and Table 1). This is consistent with a previous report by Yin et al (22) demonstrating that inhibition of EGFR by apigenin reduced ERK phosphorylation and induced G 2 -M arrest in MCF-7 and MDA468 cells. A delayed G 2 -M transition by dominant negative MAPKK1 was also reported in fibroblasts (23), further supporting our observation.…”

Section: Discussionsupporting

confidence: 94%

Loss of HSulf-1 Expression Enhances Autocrine Signaling Mediated by Amphiregulin in Breast Cancer

Narita

Chien

Mullany

et al. 2007

Journal of Biological Chemistry

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Heparan sulfate (HS) glycosaminoglycans are the oligosaccharide chains of heparan sulfate proteoglycans. The sulfation of HS glycosaminoglycan residues is required for its interaction with various heparin-binding growth factors to promote their biological activities to activate their high affinity receptor tyrosine kinases. We have identified HS glycosaminoglycan-6-O-endosulfatase HSulf-1 as a down-regulated gene in ovarian, breast, and several other cancer cell lines. Here we have shown that HSulf-1 inhibits autocrine activation of the EGFR-ERK (epidermal growth factor receptor-extracellular signal-regulated kinase) pathway induced by serum withdrawal in MDA-MB-468 breast cancer cells. Short hairpin RNA-mediated down-regulation of HSulf-1 in HSulf-1 clonal lines of MDA-MB-468 led to a significant increase in autocrine activation of ERK compared with vector only control. The autocrine signaling was also inhibited with neutralization antibodies against amphiregulin and HB-EGF, the heparin-binding growth factor family of the EGF superfamily. Furthermore, HSulf-1-mediated inhibition of autocrine signaling was associated with reduced cyclin D1 levels, leading to decreased S phase fraction and increased G 2 -M fraction, as well as increased cell death. Finally, evaluation of HSulf-1 expression levels in primary invasive breast tumors by RNA in situ hybridization indicated that HSulf-1 is down-regulated in the majority (60%) of tumors, with a predominant association with lobular histology. These data suggest a potential role of HSulf-1 down-regulation in mammary carcinogenesis.Breast cancer is the most common type of cancer among women in the United States. Despite the advances in early detection and therapeutic treatment options, an estimated 215,000 new cases and 41,000 deaths were reported in 2006 (1). One of the molecular signatures known to be associated with poor prognosis is the epidermal growth factor receptor (EGFR).2 The EGFR expression in breast cancer is often associated with resistance to endocrine hormone therapy (2, 3). Recent studies also indicate that hormone-induced estrogen receptor (ER) activation leads to activation of EGFR, suggesting that cross-talk between the two signaling pathways may be a crucial drug-resistant mechanism in ER-positive breast tumors (4). In addition, gene expression profiling studies identified the basal-like tumor as one of the breast tumor subtypes characterized with EGFR expression and poor prognosis (5, 6). EGFR signaling is induced by various EGF-like growth factor family ligands, such as EGF, amphiregulin, heparin-binding EGF-like growth factor (HB-EGF), betacellulin, epiregulin, and transforming growth factor-␣ (7). Amphiregulin is one of the most investigated EGFR ligands in relation to breast cancer. Amphiregulin is a heparin-binding growth factor that requires heparan sulfate (HS) glycosaminoglycans as a low affinity coreceptor (8) and is overexpressed in the majority of primary breast tumors (9). Expression of amphiregulin and EGFR are seen both in breast tumors a...

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Section: Discussionsupporting

confidence: 94%

Loss of HSulf-1 Expression Enhances Autocrine Signaling Mediated by Amphiregulin in Breast Cancer

Narita

Chien

Mullany

et al. 2007

Journal of Biological Chemistry

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“…Mutations in Rb are prevalent in 20% of human breast cancers and p53 mutations͞alterations are detected in Ϸ50% of primary human breast tumors (17,18), suggesting that inactivation of these two tumor suppressors may be critical in human breast tumorigenesis. The estrogen receptor-negative human breast cancer cell line MDA-MB-468 is Rb negative, harbors mutant p53, overexpresses the EGF receptor (19), and is highly responsive to MIS treatment in vitro (20). Thus testing the efficacy of MIS in severe combined immunodeficient (SCID) mice bearing MDA-MB-468 tumors would validate the antitumor studies in the C3(1)Tag model for spontaneous mammary carcinoma.…”

Section: Mullerian Inhibiting Substance (Mis) Inhibits Breast Cancer mentioning

confidence: 99%

Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model

Gupta

Carey

Kawakubo

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Mullerian inhibiting substance (MIS) inhibits breast cancer cell growth in vitro.To extend the use of MIS to treat breast cancer, it is essential to test the responsiveness of mammary tumor growth to MIS in vivo. Mammary tumors arising in the C3(1) T antigen mouse model expressed the MIS type II receptor, and MIS in vitro inhibited the growth of cells derived from tumors. Administration of MIS to mice was associated with a lower number of palpable mammary tumors compared with vehicle-treated mice (P ‫؍‬ 0.048), and the mean mammary tumor weight in the MIS-treated group was significantly lower compared with the control group (P ‫؍‬ 0.029). Analysis of proliferating cell nuclear antigen (PCNA) expression and caspase-3 cleavage in tumors revealed that exposure to MIS was associated with decreased proliferation and increased apoptosis, respectively, and was not caused by a decline in T antigen expression. The effect of MIS on tumor growth was also evaluated on xenografted human breast cancer cell line MDA-MB-468, which is estrogen receptor-and retinoblastoma-negative and expresses mutant p53, and thus complements the C3(1)Tag mouse mammary tumors that do not express estrogen receptor and have functional inactivation of retinoblastoma and p53. In agreement with results observed in the transgenic mice, MIS decreased the rate of MDA-MB-468 tumor growth and the gain in mean tumor volume in severe combined immunodeficient mice compared with vehicle-treated controls (P ‫؍‬ 0.004). These results suggest that MIS can suppress the growth of mammary tumors in vivo.proliferation ͉ apoptosis ͉ simian virus 40 large T antigen M ullerian inhibiting substance (MIS) is a member of the TGF-␤ family, a class of molecules that govern a myriad of cellular processes including growth, differentiation, and apoptosis. Synthesis of MIS demonstrates a sexually dimorphic pattern and is produced by Sertoli cells of the fetal and adult testis and granulosa cells of the postnatal ovary. In male embryos, MIS causes regression of the Mullerian duct, the anlagen of the Fallopian tubes, uterus, and upper vagina (1). However, a postnatal role for MIS in males and females has yet to be defined. Signaling by MIS is propagated by binding of MIS to the MIS type II receptor, a transmembrane serine, threonine kinase expressed at high levels in the Mullerian duct, Sertoli cells, and granulosa cells of the embryonic and adult gonads and in the uterus (2-4). The MIS-bound type II receptor subsequently recruits a type I receptor. Activin-like kinase 2 (ALK2), ALK3, and ALK6 have been implicated in mediating MIS signaling in cells (5-9).We recently demonstrated the presence of MIS receptors in mammary tissue and breast cancer cell lines, suggesting that the mammary gland is a likely target for MIS (6,10,11). In the rat mammary gland, expression of the MIS type II receptor is suppressed during puberty when the ductal system branches and invades the adipose stroma and during massive expansion at pregnancy and lactation, but is up-regulated during involution, a ti...

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“…Thus, we employed two more selective inhibitors of CK2: apigenin (also known as chrysin), a flavonoid antioxidant (Critchfield et al, 1996(Critchfield et al, , 1997; and emodin, an anthraquinone (Battistutta et al, 2000;Yim et al, 1999). Though not completely specific (Agullo et al, 1997;Lin et al, 1997;Reddy et al, 1999;Yin et al, 1999), CK2 is one of the few targets they are known to share, and thus phosphorylation reactions in which GTP can be employed that are blocked by these two chemically unrelated inhibitors are likely to be mediated by CK2. They are effective inhibitors of CK2 in vitro (Figure 1) and when used on intact cells in culture.…”

Section: Ck2 Phosphorylates a C-myc-gst Fusion Protein In Vitromentioning

confidence: 99%

Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis

2002

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Protein kinase CK2 (formerly casein kinase II) is frequently upregulated in human cancers, and transgenic expression of CK2a in lymphocytes is oncogenic. Lymphomagenesis is dramatically acclerated by coexpression of a c-myc transgene, suggestive of a synergistic interaction between the kinase and the transcription factor. Since c-myc can be phosphorylated by CK2, we hypothesized that the synergy between CK2 and c-myc might be due to a functional interaction of the two molecules. Pharmacologic inhibition of CK2 activity in cell lines established from CK2a transgenic T cell lymphomas reduces their proliferation and concomitantly with this, the steady state levels of c-myc protein decline. This is caused by acclerated c-myc protein turnover, which occurs in a proteasome-dependent manner. Transfection of cells with sense or anti-sense CK2 constructs modulates c-myc protein levels in concert with the alteration in CK2 activity, validating the findings obtained using the kinase inhibitors. Thus, CK2 is a critical regulator of c-myc protein stability and of the proliferation of these T cell lymphomas.

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Growth Inhibitory Effects of Flavonoids in Human Thyroid Cancer Cell Lines

Cited by 105 publications

References 31 publications

Loss of HSulf-1 Expression Enhances Autocrine Signaling Mediated by Amphiregulin in Breast Cancer

Loss of HSulf-1 Expression Enhances Autocrine Signaling Mediated by Amphiregulin in Breast Cancer

Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model

Functional interaction of protein kinase CK2 and c-Myc in lymphomagenesis

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