Estrogen Withdrawal-Induced NF-κB Activity and Bcl-3 Expression in Breast Cancer Cells: Roles in Growth and Hormone Independence

Pratt, M.A. Christine; Bishop, Tanya E.; White, David; Yasvinski, Gordon; Ménard, Michel; Niu, Min; Clarke, Robert

doi:10.1128/mcb.23.19.6887-6900.2003

Cited by 104 publications

(123 citation statements)

References 54 publications

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“…On the other hand, most of the benign tissues showed lower NF-κB nuclear localization (<10%) and lower MI (<0.1%). These findings permit us to conclude a positive correlation between MGT malignancy and NF-κB nuclear expression, which supports the results of previous studies in canine MGTs [29] and in human breast cancers [10,24]. In the present study, 9 of 25 dogs had multiple masses in their mammary glands.…”

Section: Discussionsupporting

confidence: 81%

Relationship between NF-κB Expression and Malignancy of Canine Mammary Gland Tumor Tissues

Mkaouar

Endo

何俊

et al. 2012

The Journal of Veterinary Medical Science

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AbSTRACT. In this study, the nuclear expression of nuclear factor kappa B (NF-κB) in 48 tissues specimens from 25 canine spontaneous mammary gland tumor (MGT) patients was assessed by immunohistochemistry to compare their levels with clinical features, histological types, prognostic outcomes and proliferative activities, including the mitotic index (MI) and cylcinD1 expression. Twelve of eighteen (66.7%) malignant tumor tissues showed greater than 10% nuclear staining, while benign tumor and hyperplastic tissues showed less than 10% nuclear staining. Higher nuclear expression of NF-κB was positively correlated with larger tumor size, lymph node metastasis and higher MI; however, no correlation was observed with distant metastasis and cyclin D1 expression. Higher NF-κB nuclear expression correlated with shorter patient survival. These findings suggest that NF-κB is a useful prognostic factor for canine MGT patients. KEY WORDS: canine MGT, immunohistochemistry, malignancy, NF-κB, prognosis.doi: 10.1292/jvms.11-0380; J. Vet. Med. Sci. 74(6): 713-718, 2012 Mammary gland tumor (MGT) is the most common type of tumor in intact female dogs [11]. The histological type of MGT tissues is strongly related to prognosis, with negative prognosis being associated with poorly differentiated tumors. Among the related factors, distant metastasis is the most significant, and dogs with distant metastasis have a worse prognosis than those with only regional lymph node involvement [15,17].Progression of breast cancer from a benign to a malignant phenotype is accompanied by overexpression of several growth factors, cytokines, and chemokines in cancer cells [22]. Some of these substances can induce the expression of prometastatic genes through nuclear factor kappa B (NF-κB) [22]. Elevated DNA binding activity of NF-κB was observed in breast cancer cell lines with invasive and metastatic growth properties [22]. The NF-κB complex is composed of a family of inducible transcription factors found in almost all cells [3,4,13], and this complex is generally recognized as an essential cell mediator acting "at the crossroads of life and death" [16]. The mammalian NF-κB family consists of 5 members: p50 (NF-κB1), p52 (NF-κB2), p65 (Rel A), c-Rel, and Rel B [23]. These Rel family members exist as homo-or heterodimers, and the most abundant form of intracellular NF-κB is generally the p50/p65 heterodimer [23]. In resting cells, NF-κB is cytoplasmically sequestered as a latent complex bound to one or more members of the IκB protein family (I-κBα, I-κBβ, I-κBε, I-κBγ, Bcl-3 and the precursor Rel proteins p100 and p105). Diverse cell stimuli induce phosphorylation (via activation of the I-κB kinase complex) and subsequent proteasomal degradation of I-κB inhibitory proteins, leading to the activation of NF-κB for nuclear translocation and DNA binding [23]. Nuclear traslocated NF-κB is reported to activate the transcription of many factors including cyclin D1, which is a key regulator of G1 checkpoint control [7,23].Information about the significance...

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Section: Discussionsupporting

confidence: 81%

Relationship between NF-κB Expression and Malignancy of Canine Mammary Gland Tumor Tissues

Mkaouar

Endo

何俊

et al. 2012

The Journal of Veterinary Medical Science

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“…11 Loss of estrogen signaling through estradiol removal likewise allows NF-B activity, which may contribute to hormone-independence of human breast cancer cells in culture. 42 ErbB2 induced cyclin D1 expression in tissue culture 27 and herein ErbB2 induced cyclin D1 in vivo via an NF-Bdependent mechanism. This was accompanied by an increase in the proportion of pRb in the phosphorylated form that is permissive for cell-cycle entry.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Factor-κB Enhances ErbB2-Induced Mammary Tumorigenesis and Neoangiogenesis in Vivo

Liu

Willmarth

et al. 2009

The American Journal of Pathology

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“…However, our results suggest that ER signaling requires NF-kB activation (Figures 2 and 5), even though other transcription factors could be activated and bound to cyclin D1 promoter (Figure 5f). Since NF-kB can be activated by multiple stimuli (Ghosh and Karin, 2002) and its constitutive activation has been found in several breast tumor cells during progression to hormoneindependent growth (Nakshatri et al, 1997;Biswas et al, 2000;Pratt et al, 2003), it can be speculated that, in a physiological context, active NF-kB is probably available at compatible levels with ER requirement during the early stages of tumor progression when cells remain responsive to estrogens. This could be occurring in cells that are still sensitive to TNF-a-induced apoptosis and even in the absence of this cytokine.…”

Section: Discussionmentioning

confidence: 99%

TNF-α enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B

et al. 2005

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Breast tumors are usually classified according to their response to estrogens as hormone-dependent or -independent. In this work, we investigated the role of the proinflammatory cytokine TNF-a on the estrogen-receptor-positive T47D breast ductal tumor cells. We have found that TNF-a exerts a mitogenic effect, inducing cyclin D1 expression and activation of the transcription factor NF-jB. Importantly, activation of NF-jB was required for estrogen-induced proliferation and cyclin D1 expression. TNF-a enhanced the estrogen response by increasing the levels and availability of NF-jB. Chromatin immunoprecipitation analysis suggested that the action of estrogens is mediated by a protein complex that contains the activated estrogen receptor, the nuclear receptor coactivator RAC3 and a member of the NF-jB family. Finally, our results demonstrate that activation of this transcription factor could be one of the key signals for estrogen-mediated response.

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Estrogen Withdrawal-Induced NF-κB Activity and Bcl-3 Expression in Breast Cancer Cells: Roles in Growth and Hormone Independence

Cited by 104 publications

References 54 publications

Relationship between NF-κB Expression and Malignancy of Canine Mammary Gland Tumor Tissues

Relationship between NF-κB Expression and Malignancy of Canine Mammary Gland Tumor Tissues

Nuclear Factor-κB Enhances ErbB2-Induced Mammary Tumorigenesis and Neoangiogenesis in Vivo

TNF-α enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B

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