Changes of survivin mRNA and protein expression during paclitaxel treatment in breast cancer cells

Huihua, Xiong; Yu, Shiying; Zeng, Liang; Xiong, Hua

doi:10.1007/s11596-007-0119-9

Cited by 13 publications

(11 citation statements)

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“…siRNA‐survivin could also increase the sensitivity of these cells to paclitaxel albeit not to the same magnitude as that observed in cells with abundant amount of survivin. Paclitaxel itself has been reported to induce survivin expression in the MCF‐7 cells40, 56 and siRNA‐survivin increases their sensitivity to paclitaxel 40. We found that paclitaxel also induces a further increase in survivin expression in the BRCA1 mutant HCC1937 cells that already express a high level of survivin.…”

Section: Discussionmentioning

confidence: 55%

See 1 more Smart Citation

BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

Promkan

Patmasiriwat

Chakrabarty

2009

Intl Journal of Cancer

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BRCA1 is a multifunctional tumor-suppressive protein. Many functional aspects of BRCA1 are not fully understood. We used a shRNA approach to probe the function of BRCA1 in human breast cancer cells. Knocking down BRCA1 expression by shRNA in the wild-type BRCA1 human breast cancer MCF-7 and MDA-MB-231 cells resulted in an increase in cell proliferation, anchorage-independent growth, cell migration, invasion and a loss of p21/Waf1 and p27 Kip1 expression. In BRCA1 knocked-down cells, the expression of survivin was significantly up regulated with a concurrent decrease in cellular sensitivity to paclitaxel. We also found that cells harboring endogenous mutant or defective BRCA1 (MDA-MB-436 and HCC1937) were highly proliferative and expressed a relatively low level of p21/Waf1 and p27 Kip1 by comparison to wild-type BRCA1 cells. Cells harboring mutated BRCA1 also expressed a high level of survivin and were relatively resistant to paclitaxel by comparison to wild-type cells. Increase resistance to paclitaxel was due to an increase in the expression of survivin in both the BRCA1 knocked-down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel. We conclude that BRCA1 down-modulates the malignant behavior of breast cancer cells, promotes the expression of p21/Waf1, p27 Kip1 and inhibits the expression of survivin. Moreover, loss of BRCA1 expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to paclitaxel. ' UICCKey words: BRCA1; p21/Waf1; p27Kip1; survivin; chemosensitivity Hereditary breast cancer can be caused by germline mutations in 1 of the 2 tumor suppressor genes, BRCA1 and BRCA2 resulting in a loss of gene function. 1,2 Women carrying 1 mutated BRCA1 allele are at increased risk of developing breast cancer but tumor initiation requires a loss of the wild-type allele indicating that BRCA1 is a tumor suppressor gene. 3,4 Hereditary breast cancers account for 5-10% of all breast cancers. 5-8 Breast cancer cumulative risk to age 50 years and 70 years in mutation carriers are 49% and 71%, respectively, for BRCA1. 9 BRCA1 expression is also frequently reduced in sporadic cancer. 10-13 BRCA1 encodes an 1863 amino acid (220 kDa) protein that is targeted to the nucleus by 2 nuclear localization sequences, which interact with the nuclear transport signal receptor. 14-17 BRCA1 protein is multifunctional and interacts with other proteins in the nucleus in transcriptional regulation of gene expression, DNA repair and in the maintenance of genomic stability. 1,18 Thus, loss of BRCA1 function may lead to accumulation of chromosomal damage, abnormalities in growth control and tumorigenesis. 19 BRCA1 is regarded as an important central component in regulating multiple biological pathways. 18,20 The function of BRCA1 intersects with the cyclin-dependent kinase inhibitor p27 Kip1 , cyclin D1, the extracellular matrix [21][22][23] and with the estrogen and progesterone pathways in hormonal driven tumor development and progres...

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Section: Discussionmentioning

confidence: 55%

“…It has been reported that treatment of the MCF‐7 cells by paclitaxel itself induces survivin expression 40, 56. In a final series of experiments, we determined if paclitaxel could induce survivin expression in the HCC1937 cells and whether siRNA‐survivin could block such induction.…”

Section: Resultsmentioning

confidence: 96%

BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

Promkan

Patmasiriwat

Chakrabarty

2009

Intl Journal of Cancer

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“…This up-regulation leads to the phosphorylation and accumulation of survivin, believed to be the downstream effector of TIS escape [57,58]. Different studies have reported that the treatment of MCF-7 cells with PTX rapidly up-regulated survivin expression within 4–6 h, in a process that was independent from G2/M arrest [59,60]. Bridget and coworkers have shown that the treatment of MDA-MB-231 cells with PTX caused them to generate exosomes highly enriched with survivin.…”

Section: Discussionmentioning

confidence: 99%

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin

2019

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Background: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present study, the short and long-term cytotoxic effects as well as migratory effects of PTX, DXR, and its combinations at 10:1; 1:1 and 1:10 PTX:DXR molar ratios either free or co-encapsulated in liposomes were evaluated against three human BC cell lines (MDA-MB-231, MCF-7, and SKBR-3). Method: The MTT assay was used to screen for synergy or antagonism between PTX and DXR and the combination index value was calculated using the CalcuSyn software. Nuclear morphological alterations were evaluated by staining the cells with Hoescht 33342. The investigation of senescence and clonogenicity of BC cell lines exposed to different treatments was also studied. In addition, the ability of these cells to migrate was assessed. Results: Taken together, the results presented herein allow us to suggest that there is no benefit in enhancing the PTX concentration above that of DXR in the combination for any of the three cell lines tested. Conclusion: The developed liposomes co-encapsulating PTX and DXR in different molar ratios retained the biological properties of the mixture of free drugs and are valuable for planning new therapeutic strategies.

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“…Recent meta-analysis of survivin expression in breast cancer patients also demonstrated a significant association between positive survivin expression and a poor overall survival consequence in breast cancer patients [40]. Decreased survivin expression was found to increase sensitivity to chemotherapy drugs [41], [42] and ionizing radiation [43]. It has been shown that estrogen upregulates the expression of survivin in ER positive MCF-7 breast cancer cells [44].…”

Section: Discussionmentioning

confidence: 98%

Expression of NgBR Is Highly Associated with Estrogen Receptor Alpha and Survivin in Breast Cancer

et al. 2013

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NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our recent findings demonstrated that NgBR binds farnesylated Ras and recruits Ras to the plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis. Here, we first use immunohistochemistry and real-time PCR approaches to examine the expression patterns of Nogo-B and NgBR in both normal and breast tumor tissues. Then, we examine the relationship between NgBR expression and molecular subtypes of breast cancer, and the roles of NgBR in estrogen-dependent survivin signaling pathway. Results showed that NgBR and Nogo-B protein were detected in both normal and breast tumor tissues. However, the expression of Nogo-B and NgBR in breast tumor tissue was much stronger than in normal breast tissue. The statistical analysis demonstrated that NgBR is highly associated with ER-positive/HER2-negative breast cancer. We also found that the expression of NgBR has a strong correlation with the expression of survivin, which is a well-known apoptosis inhibitor. The correlation between NgBR and survivin gene expression was further confirmed by real-time PCR. In vitro results also demonstrated that estradiol induces the expression of survivin in ER-positive T47D breast tumor cells but not in ER-negative MDA-MB-468 breast tumor cells. NgBR knockdown with siRNA abolishes estradiol-induced survivin expression in ER-positive T47D cells but not in ER-negative MDA-MB-468 cells. In addition, estradiol increases the expression of survivin and cell growth in ER-positive MCF-7 and T47D cells whereas knockdown of NgBR with siRNA reduces estradiol-induced survivin expression and cell growth. In summary, these results indicate that NgBR is a new molecular marker for breast cancer. The data suggest that the expression of NgBR may be essential in promoting ER-positive tumor cell proliferation via survivin induction in breast cancer.

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Changes of survivin mRNA and protein expression during paclitaxel treatment in breast cancer cells

Cited by 13 publications

References 5 publications

BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin

Expression of NgBR Is Highly Associated with Estrogen Receptor Alpha and Survivin in Breast Cancer

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