Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas

Sierra, Àngels; Castellsagué, Xavier; Escobedo, A.; Moreno, Abelardo; Drudis, Teresa; Fabra, Àngels

doi:10.1023/a:1006120006471

Cited by 27 publications

(14 citation statements)

References 19 publications

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“…Previous studies also suggest that ROCK is implicated in the regulation of c-Myc (25,27,28). c-Myc plays a pivotal role in modulating cell division and transformation (29,30), and clinical studies have shown a strong association between overexpression of c-Myc and tumor metastasis (31)(32)(33). In our study, the c-Myc level was significantly increased in MDA-MB-231 and SUM1315 cells compared with MCF-7 cells in vitro ( Fig.…”

Section: Resultssupporting

confidence: 76%

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Inhibition of Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone

et al. 2009

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Rho-associated kinase (ROCK) signaling plays a fundamental role in regulating cell morphology, adhesion, and motility. Aberrant expression of ROCK is related to tumor metastases and poor clinical outcome. Here, we show that ROCK expression is increased in metastatic human mammary tumors and breast cancer cell lines compared with nonmetastatic tumors and cell lines. Overexpression of ROCK confers a metastatic phenotype on the nonmetastatic MCF-7 cell line. Inhibition of ROCK activity, by either a specific ROCK inhibitor (Y27632) or ROCK-targeted small interfering RNAs, reduces cell migration and proliferation in vitro and metastasis to bone in vivo using a novel "human breast cancer metastasis to human bone" mouse model. Expression of the c-Mycregulated miR-17-92 cluster is shown to be elevated in metastatic breast cancer cells compared with nonmetastatic cells and diminished by Y27632 treatment. Furthermore, blockade of miR-17 is shown to decrease breast cancer cell invasion/ migration in vitro and metastasis in vivo. Together, these findings suggest that augmented ROCK signaling contributes to breast cancer metastasis. The effects of ROCK on tumor cell invasion/motility and growth may derive from regulating cytoskeletal actin-myosin contraction and modulating the c-Myc pathway, including c-Myc-dependent microRNAs. Inhibition of ROCK or the pathway it stimulates, therefore, may represent a novel approach for treatment of breast cancer metastases. [Cancer Res 2009;69(22):8742-51]

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Section: Resultssupporting

confidence: 76%

“…Many studies have shown that c-Myc is amplified and/or overexpressed in breast cancer (34,45), particularly in late-stage/ high-grade tumors and metastatic tumors (31)(32)(33). Its aberrant expression appears to be a clinical prognostic marker for recurrence and adverse outcomes in breast cancer patients (46,47).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone

et al. 2009

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“…A study by Janocko et al (1995) found a preferential sequence for gene amplification in breast cancer, with c-myc most often occurring first, followed by c-erbB-2. Sierra et al (1999) demonstrated in breast cancer patients that Bcl-2 overexpression was strongly associated with lymph node metastasis, but only when c-myc was co-expressed. Caspase 9 is a downstream cofactor in myc-dependent tumourigenesis and progression.…”

Section: Amplification Of C-myc In Relation To Other Oncogenesmentioning

confidence: 99%

C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance

et al. 2000

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Data from basic research suggests that amplification of the proto-oncogene c-myc is important in breast cancer pathogenesis, but its frequency of amplification and prognostic relevance in human studies have been inconsistent. In an effort to clarify the clinical significance of c-myc amplification in breast cancer, we conducted a comprehensive literature search and a meta-analysis in which 29 studies were evaluated. The weighted average frequency of c-myc amplification in breast tumours was 15.7% (95% CI = 12.5–18.8%), although estimates in individual studies exhibited significant heterogeneity, P < 0.0001. C-myc amplification exhibited significant but weak associations with tumour grade (RR = 1.61), lymph-node metastasis (RR = 1.24), negative progesterone receptor status (RR = 1.27), and postmenopausal status (RR = 0.82). Amplification was significantly associated with risk of relapse and death, with pooled estimates RR = 2.05 (95% CI = 1.51–2.78) and RR = 1.74 (95% CI = 1.27–2.39), respectively. This effect did not appear to be merely a surrogate for other prognostic factors. These results suggest that c-myc amplification is relatively common in breast cancer and may provide independent prognostic information. More rigorous studies with consistent methodology are required to validate this association, and to investigate its potential as a molecular predictor of specific therapy response. © 2000 Cancer Research Campaign http://www.bjcancer.com

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“…Aberrant regulation and overexpression of c-Myc are observed in most tumor types, and the c-Myc signaling is believed to play a critical role in oncogenesis (4)(5)(6)(7). A large body of studies have shown that c-Myc is pathologically amplified and/or overexpressed in breast cancers (8,9), particularly in late-stage tumors (10)(11)(12). Its activation seems to be a prognostic marker in predicting recurrence and adverse outcomes in patients with breast cancer (5)(6)(7)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis

Zhang

Yin

Wang

et al. 2014

Molecular Cancer Research

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Activation of c-Myc plays a decisive role in the development of many human cancers. As a transcription factor, cMyc facilitates cell growth and proliferation by directly transcribing a multitude of targets, including rRNAs and ribosome proteins. However, how to elucidate the deregulation of rRNAs and ribosome proteins driven by c-Myc in cancer remains a significant challenge and thus warrants close investigation. In this report, a crucial role for the HSPC111 (NOP16) multiprotein complex in governing ribosomal biogenesis and tumor growth was determined. It was discovered that enhanced HSPC111 expression paralleled the upregulation of c-Myc and was directly regulated by c-Myc in breast cancer cells. Knockdown of HSPC111 dramatically reduced the occurrence of tumorigenesis in vivo, and largely restrained tumor cell growth in vitro and in vivo. In stark contrast, HSPC111 overexpression significantly promoted tumor cell growth. Biochemically, it was demonstrated that RNA 3 0 -phosphate cyclase (RTCD1/RTCA) interacted with HSPC111, and RTCD1 was involved in the HSPC111 multiprotein complex in regulating rRNA production and ribosomal biogenesis. Moreover, HSPC111 and RTCD1 synergistically modulated cell growth and cellular size through commanding rRNA synthesis and ribosome assembly coupled to protein production. Finally, overall survival analysis revealed that concomitant upregulation of HSPC111 and RTCD1 correlated with the worst prognosis in a breast cancer cohort.Implications: Inhibition of HSPC111-dependent ribosomal biosynthesis and protein synthesis is a promising therapeutic strategy to diminish breast cancer tumor progression. Mol Cancer Res; 12(4); 583-94. Ó2014 AACR. IntroductionBreast cancer is by far the most common cancer among women and the leading cause of cancer-related deaths worldwide. The primary tumor and metastases to distant organs often cause significant morbidity and mortality. Numerous studies suggest that the oncogene c-Myc plays a crucial role in the development and progression of breast cancer. Along with its partner protein Max, c-Myc regulates an estimated 10% to 15% of genes in the human genome, and globally reprograms cells and drives proliferation (1-3). Aberrant regulation and overexpression of c-Myc are observed in most tumor types,

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Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas

Cited by 27 publications

References 19 publications

Inhibition of Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone

Inhibition of Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone

C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance

HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis

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