Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer

Aaltonen, Kirsimari; Amini, Rose‐Marie; Landberg, Göran; Eerola, Hannaleena; Aittomäki, Kristiina; Heikkilä, Päivi; Nevanlinna, Heli; Blomqvist, Carl

doi:10.1007/s10549-008-9908-5

Cited by 55 publications

(70 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ad di ti o nally, Ru das et al 37 ha ve emp ha si zed that cyclin D1 ex pres si on affected pa ti ent's prognos tic fac tors. Si mi larly, in the study per for med by Aal to nen et al 38 it is re por ted that cyclin D1 expres si on had ad ver se ef fects on prog no sis. Ho wever, on the con trary, Pe na ult-Llor ca et al 39 did not find a sta tis ti cally sig ni fi cant re la ti on in pa ti ents bet we en with cyclin D1 ex pres si on and di se a sefre e and ove rall sur vi val.…”

Section: Discussionmentioning

confidence: 96%

β-Catenin Stability, Cyclin D1 and Frizzled Proteins Expression in Human Breast Cancer and Their Relation with the Prognosis

Zengel¹,

Vardar²,

Postacı³

et al. 2011

Turkiye Klinikleri J Med Sci

View full text Add to dashboard Cite

A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Aberrant Wnt signaling pathway activation and stabilization of β-catenin protein is associated with tumorigenesis and human breast tumors. We have examined β-catenin, cyclin D1, sFRP1 and sFRP2 expressions in the breast cancer and effects of these factors on prognostic parameters in patients with breast cancer. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : One hundred and seventeen consecutive female malignant breast tumor patients were enrolled into the study. The mean age was 50.0 (±18.0) years. Immunohistochemical staining method was used to investigate the stability and location of β-catenin, expressions of sFRP1 and sFRP2 and cyclin D1 proteins. R Re es su ul lt ts s: : Percentage expression of β-catenin, siklin D1, sFRP1 and sFRP2 were 60.0 ± 55.0, 40.0 ± 64.0, 15.0±48.0 and 25.0 ± 53.0, respectively. Menopausal status, progesterone receptor positivity, lymph node involvement and TNM staging did not show any statistically significant relation with the expression of β-catenin, cyclin D1, sFRP1 or sFRP2. However, significantly higher percentages of expression of cyclin D1 were determined in patients showing estrogen receptor positivity and cerbB-2 over-expression (p= 0.008). Additionally β-catenin expression was significantly higher only in the p53-positive group (p= 0.03). None of the parameters used in this study showed a significant effect on clinicopathological prognostic parameters. C Co on nc cl lu us si io on n: : These findings suggested that expression levels and staining results of β-catenin, cyclinD1, sFRP1 and sFRP2 in tumor cells were independent from histological grade, lymph node involvement, and TNM stage. We concluded that β-catenin accumulation, cyclin D1, sFRP1 and sFRP2 expressions were not affected by the Wnt signaling pathway. K Ke ey y W Wo or rd ds s: : Breast neoplasm; β-catenin; cyclin D1; secreted frizzled related proteins Ö ÖZ ZE ET T A Am ma aç ç: : Wnt sinyal yolağının aberan aktivasyonu ve β-katenin proteininin stabilizasyonu tümör gelişimi ve insan meme tümörleri ile ilişkilidir. Bu çalışmada, meme kanserinde β-katenin, siklin D1, sFRP1 ve sFRP2 ekspresyonlarını ve bu faktörlerin hastaların prognostik parametreleri üzerine etkilerini incelemeyi amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Ortalama yaşı 50 ± 18 olan ardışık 117 meme kanserli kadın olgu çalışmaya alındı. İmmünositokimyasal yöntemle β-katenin stabilitesi, sFRP1, sFRP2 ve siklin D1 proteinlerinin ekspresyonları değerlendirildi. B Bu ul lg gu ul la ar r: : β-katenin, siklin D1, sFRP1 ve sFRP2'nin ekspresyonları sırasıyla %60.0 (±55.0), %40.0 (±64.0), %15.0 (±48.0) ve %25.0 (±53.0) idi. Menopozal durum, progesteron reseptörü, lenf nodu tutulumu, TNM evresi ile β-katenin, siklin D1, sFRP1 veya sFRP2 ekspresyonu arasında istatistiksel olarak anlamlı bir ilişki bulunmadı. Bununla birlikte olgularda östrojen pozitifliği ve cerbB-2 pozitifliği ile siklin D1 arasında istatistiksel olarak anlamlı ilişki varlığı izlendi (p= 0.008). β-...

show abstract

Section: Discussionmentioning

confidence: 96%

β-Catenin Stability, Cyclin D1 and Frizzled Proteins Expression in Human Breast Cancer and Their Relation with the Prognosis

Zengel¹,

Vardar²,

Postacı³

et al. 2011

Turkiye Klinikleri J Med Sci

View full text Add to dashboard Cite

show abstract

“…The role of cyclin D1 in breast cancer prognosis remains unclear. Some studies have shown a correlation between cyclin D1 expression and poor or good prognosis, while some showed no correlation between them [1,2,14,26,28]. Experimental data implied that cyclin D1 was needed to drive proliferation in estrogen receptor (ER)-positive breast cancer cells, while in ER-negative breast cancer cells, cell proliferation proceeds through other cyclin D1-independent mechanisms [20].…”

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

“…Cyclin D1 is overexpressed in nearly 50% of breast cancers and a well-defined target of E2-mediated signaling in ER-positive cancer cells such as MCF-7 (27). In MCF-7 cells, treatment of G0/G1-arrested cells with E2 significantly upregulates cyclin D1 mRNA and protein expression (28). In addition, E2 modulates the function of cell cycle regulators such as p21, p27 and p16 (29).…”

Section: Effects Of E2 Bpa or MXC On Cyclin D1 And P21 Expression Inmentioning

confidence: 99%

Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway

Choi

2012

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Various endocrine disrupting chemicals (EDCs) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane [methoxychlor (MXC)] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors (ERs), causing human health problems such as abnormal reproduction and carcinogenesis. In this study, we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells. MCF-7 cells are known to be ERα-positive and to be a highly E2-responsive cancer cell line; these cells are, therefore, a useful in vitro model for detecting estrogenic activity in response to EDCs. We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay. We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH. To determine whether BPA and MXC stimulate cancer cell growth though ER signaling, we co-treated the cells with agonists (propyl pyrazoletriol, PPT; and diarylpropionitrile, DPN) or an antagonist (ICI 182,780) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells before treatment with EDCs. These studies confirmed the carcinogenicity of EDCs in vitro. As a result, BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes, especially ones affecting the G1/S transition via ERα signaling. These collective results confirm the carcinogenicity of these EDCs in vitro. Further studies are required to determine whether EDCs promote carcinogenesis in vivo.

show abstract

Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer

Cited by 55 publications

References 42 publications

β-Catenin Stability, Cyclin D1 and Frizzled Proteins Expression in Human Breast Cancer and Their Relation with the Prognosis

β-Catenin Stability, Cyclin D1 and Frizzled Proteins Expression in Human Breast Cancer and Their Relation with the Prognosis

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

Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway

Contact Info

Product

Resources

About