p185neu protein is required for tumor and anchorage‐independent growth, not for cell proliferation of transgenic mammary carcinoma

Nanni, Patrizia; Pupa, Serenella M.; Nicoletti, Giordano; Giovanni, Carla De; Landuzzi, Lorena; Rossi, Ilaria; Astolfi, Annalisa; Ricci, Cinzia; Vecchi, R.; Invernizzi, Anna M.; Carlo, Emma Di; Musiani, Piero; Forni, Guido; Ménard, Sylvie; Lollini, Pier‐Luigi

doi:10.1002/1097-0215(20000715)87:2<186::aid-ijc5>3.3.co;2-t

Cited by 31 publications

(44 citation statements)

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“…or i.t. [27][28][29] The anti-tumor activity of aerosol-delivered CpG-ODN was evaluated in two murine tumor models with different characteristics and behavior: the mammary carcinoma N202.1A is highly immunogenic due to overexpression of the heterologous rat neu oncogene, 25 while the B16 melanoma is poorly immunogenic and reportedly expresses very low levels of MHC I molecules. 42 These two tumors also differ in their sensitivity to immune effectors, with the neu-expressing mouse mammary tumor sensitive to cytotoxic activity of T but not NK cells, 43 while NK cells are required to counteract the growth of B16 melanomas.…”

Section: Discussionmentioning

confidence: 99%

“…N202.1A cells, derived from a spontaneous mammary carcinoma in an FVB-neuN transgenic mouse, 25 and B16 mouse melanoma cells were routinely maintained at 37 C in a 5% CO 2 atmosphere in Roswell Park Memorial Institute medium 1640 and Dulbecco's modified Eagle's Medium, respectively, supplemented with 10% fetal calf serum and 2 mM glutamine. Purified, phosphorothioated ODN1826 (5 0 -TCCAT-GACGTT CCTGACGTT-3 0 ) containing CpG motifs was synthesized by TriLink Biotechnologies (San Diego, CA).…”

Section: Cell Lines and Reagentsmentioning

confidence: 99%

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Anti‐tumor activity of CpG‐ODN aerosol in mouse lung metastases

Sfondrini

Sommariva

Tortoreto

et al. 2013

Intl Journal of Cancer

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Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-c and IL-1b and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD41 cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Lines and Reagentsmentioning

confidence: 99%

Anti‐tumor activity of CpG‐ODN aerosol in mouse lung metastases

Sfondrini

Sommariva

Tortoreto

et al. 2013

Intl Journal of Cancer

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“…N202/1A was found to express high levels of p185 neu , whereas this expression was not detectable in N202/1E cells. 20 SKBr3 is a human breast adenocarcinoma cell line overexpressing human HER-2/neu. Confluent monolayers (5 Â 10 5 cells/cm 2 ) of the tumor cell lines were treated with a 0.25% solution of trypsin in PBS and used for in vitro experiments.…”

Section: Tumor Cell Linesmentioning

confidence: 99%

Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Provinciali

Donnini

et al. 2005

Intl Journal of Cancer

113

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Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER-2/neu in tumoral mammary glands from Res-treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors (p < 0.001), reduced the mean number and size of mammary tumors (p < 0.0001) and diminished the number of lung metastases in HER-2/neu transgenic mice. The effects of Res were associated with downregulation of HER-2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL-2-induced NK activity nor the lymphocyte number and proliferation was modified in Res-supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER-2/neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER-2/neu expression and the induction of apoptosis in tumor cells. ' 2005 Wiley-Liss, Inc.Key words: resveratrol; HER-2/neu; mammary tumor; transgenic mouse; apoptosis Cancer chemoprevention, the prevention of cancer by chemical agents that reduce the risk of carcinogenesis, is one of the most direct ways to reduce morbidity and mortality. Res (trans-3,4 0 , 5-trihydroxystilbene) is a naturally occurring polyphenolic antioxidant compound present in grapes, mulberries, peanuts and red wine. It has been identified as an excellent candidate cancer chemopreventive, based on its safety and efficacy in experimental models of carcinogenesis. It has been found to inhibit diverse cellular events associated with tumor initiation, promotion and progression. 1 Most of the antitumor activity of Res has been discovered through in vitro studies in tumor cell lines. In these studies, Res was generally found to induce growth inhibition and apoptosis of a panel of human and murine tumor cell lines. [2][3][4][5][6][7] Fewer studies have been conducted on the antitumor effect exerted by in vivo supplementation with Res. Res was found to inhibit tumorigenesis in a mouse skin cancer model. 1 In other studies, it protected rats from ascites hepatoma 8 and colon carcinogenesis 9 and exerted inhibitory effects on tumor growth and lung metastasis in mice bearing highly metastatic Lewis lung carcinoma. 10 In the latter study, the effect of Res was related to its proapoptotic and antiangiogenic action on tumor cells, with no evidence of modulation of the immune response. 10 Res also inhibited the growth of experimentally implante...

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“…13,25 Two HER-2/neu-positive cell clones (N202.1A and TT12.E2, hereafter referred to as Neu/A and Neu/B) and one HER-2/neu-negative cell clone (N202.1E, a brother clone of N202.1A, hereafter referred to as Neu neg /A) were used. Cells were cultured in Dulbecco's modified Eagle's medium supplemented with 20% fetal bovine serum (Invitrogen, Milan, Italy).…”

Section: Cell Linesmentioning

confidence: 99%

Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma

Astolfi

Landuzzi

Nicoletti

et al. 2005

The American Journal of Pathology

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We previously showed that a vaccine combining interleukin 12 and allogeneic p185 neu Immunological prevention of tumors is a feasible possibility especially in light of both the encouraging results obtained in preclinical models of neoplasia and of the recent advances in detection of healthy individuals at high risk of developing cancer. 1,2 Transgenic mice expressing the HER-2/neu oncogene under tissue-specific transcriptional control of the mouse mammary tumor virus promoter (MMTV-LTR) represent a suitable model of mammary carcinogenesis. HER-2/neu is overexpressed in 25 to 30% of human breast cancers, influencing biological features and prognosis of the tumor, and the natural history of HER-2/neu transgenic mammary tumors closely resembles that of human breast carcinoma, from atypical hyperplasia to carcinoma in situ and invasive tumor. 3 Among HER-2/neu transgenic mice, BALB-NeuT mice harboring a mutated version of the rat neu oncogene represent a very aggressive model of mammary carcinogenesis because they develop multifocal mamSupported by the

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p185neu protein is required for tumor and anchorage‐independent growth, not for cell proliferation of transgenic mammary carcinoma

Cited by 31 publications

References 0 publications

Anti‐tumor activity of CpG‐ODN aerosol in mouse lung metastases

Anti‐tumor activity of CpG‐ODN aerosol in mouse lung metastases

Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice

Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma

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