Significance of survivin and Bcl-2 homologous antagonist/killer mRNA in detection of bone metastasis in patients with breast cancer

Zohny, Samir F.; El-Shinawi, Mohamed

doi:10.1007/s12032-010-9724-8

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…[ 20 21 ] Recently, survivin, a member of the inhibitor of apoptosis family, along with birc3 was shown to be a considerable marker in the identification of breast cancer metastasis. [ 22 ] Further, survivin has been determined to be a prognostic marker and therapeutic target for metastatic prostate cancer. [ 23 ] Therefore, the down-regulation of survivin and its family member birc3 may prove to have significant clinical benefits.…”

Section: Discussionmentioning

confidence: 99%

Zoledronic acid directly suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers

Almubarak¹,

Jones²,

Chaisuparat³

et al. 2011

J Carcinog

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Background:Bisphosphonates (BPs) were designed for the prevention of skeletal-related events secondary to bone metastases. The purpose of this study was to show that zoledronic acid (ZA) directly eradicates highly tumorigenic and potentially metastatic cancer cells.Materials and Methods:Human prostate and breast highly tumorigenic (PC3, MCF 7) and low- or non-tumorigenic (LNCaP, MCF 10a) cell lines, respectively, were exposed to different concentrations of ZA (0-10 μM). Reverse transcriptase double quantitative polymerase chain reaction was used for quantitative gene expression analysis. Apoptosis and cell proliferation were determined using microscopic observation and MTS assays. Western blot was used to confirm the translational effects of apoptotic genes on protein expression.Results:Human prostate and breast highly tumorigenic (PC3, MCF 7) and low- or non-tumorigenic (LNCaP, MCF 10a) cell lines, respectively, showed multiple genes demonstrating differential expressions, including TRAF, TRADD, BCL2, CASPASES and IAP families. Increasing ZA concentrations showed a greater concentration-time response on cell proliferation and apoptosis in the highly tumorigenic cells. These results were confirmed by both reversing and enhancing the effect of ZA on cell proliferation with caspase 3, 7 or survivin siRNA, respectively. Pro-apoptotic proteins bax and caspase 2, 3, 7 and 9 were up-regulated, while the anti-apoptotic proteins bcl2, birc3 and survivin were down-regulated only in the highly tumorigenic cells.Conclusions:This explains the ability of ZA to inhibit bony metastasis in highly tumorigenic cells compared with the low- or non-tumorigenic cells through a significant decrease in cell proliferation and increase in apoptosis through gene-regulated and translational-mediated down-regulation of survivin coupled with the inhibition of caspase 3 or 7. This has significant implications toward understanding the pharmacophysiology of BPs in metastasis and supports the clinically observed effect of BPs when administered adjunctively with anticancer drugs such as cyclophosphamide/methotrexate/5-fluorouracil, epirubicin in combination with cyclophosphamide or docetaxel, and doxorubicin.

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Section: Discussionmentioning

confidence: 99%

Zoledronic acid directly suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers

Almubarak¹,

Jones²,

Chaisuparat³

et al. 2011

J Carcinog

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“…Our recent studies have shown that, in prostate cancer, Survivin levels are regulated by oxidative stress and are particularly high in metastatic tissues as compared to primary tumors [115], a result in line with previous studies implicating Survivin as a mediator of tumor metastasis to bone [176]. Further testimony to its potential role in bone metastatic disease are the reports on significantly higher Survivin levels in patients with skeletal lesions from breast cancer as compared to patients with non-metastatic or benign disease [177].…”

Section: Life Vs Death Decision-making: Anti-apoptosis and Pro-survisupporting

confidence: 71%

The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone

Diedrich

Herroon

Rajagurubandara

et al. 2018

Curr Osteoporos Rep

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The combined in silico, pre-clinical, and clinical evidence shows that in adipocyte-rich tissues such as bone marrow, tumor cells rely on exogenous lipids for regulation of cellular energetics and adaptation to harsh metabolic conditions of the metastatic niche. Adipocyte-supplied lipids have a potential to alter the cell's metabolic decisions by regulating glycolysis and respiration, fatty acid oxidation, lipid desaturation, and PPAR signaling. The downstream effects of lipid signaling on mitochondrial homeostasis ultimately control life vs. death decisions, providing a mechanism for gaining survival advantage and reduced sensitivity to treatment. There is a need for future research directed towards identifying the key metabolic and signaling pathways that regulate tumor dependence on exogenous lipids and consequently drive the pro-survival behavior in the bone marrow niche.

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“…Zohny and El-Shinawi [18] reported that Bak mRNA was markedly decreased in bone metastatic patients compared to nonmetastatic patients; however, significant expression of Bak mRNA was observed in bone metastatic cases compared to benign patients. In contrast, in the present study, N2 shows a significant increase in Bak mRNA opposite to N0 or N1.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Bax and Bak Gene Mutations and Expression in Breast Cancer

Kholoussi

El-Nabi

Esmaiel

et al. 2014

BioMed Research International

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Genetic analyses have provided evidence to suggest that Bax and Bak are the essential genes for apoptosis in mammalians cells. This study aimed to search for biomarkers in breast cancer to be used as prognostic markers for the disease. The Bak and Bax genes expressions were analyzed in 23 breast cancer patients by RT-PCR technique. SSCP technique was used to detect the mobility of the abnormal fragment in Bak exon 4. PCR for Bax promoter was digested with Tau 1 restriction enzyme to identify a single polymorphism G(-248)A. The expression of Bak gene is related to several clinical factors of breast cancer. The analysis of Bax RNA showed 4 isoforms of Bax with different distributions in the normal and tumor tissues. These isoforms were Bax α, d, δ, and ζ. Exon 4 had a normal pattern in all cases of breast cancer. There was a statistically significant difference in the frequency distribution of the G(-248)A genotypes in the breast cancer tissues with grade 3+high, T2 stage, lobular +other, and PR −ve subgroups. In this study, Bak expression seems to lead to development of breast cancer and affects the disease progression. Also, Bax d and Bax δ could be used as risk factor and biomarker for breast cancer with the distribution of G284A.

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Significance of survivin and Bcl-2 homologous antagonist/killer mRNA in detection of bone metastasis in patients with breast cancer

Cited by 5 publications

References 28 publications

Zoledronic acid directly suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers

Zoledronic acid directly suppresses cell proliferation and induces apoptosis in highly tumorigenic prostate and breast cancers

The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone

Evaluation of Bax and Bak Gene Mutations and Expression in Breast Cancer

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