BRCA1 suppresses the expression of survivin and promotes sensitivity to paclitaxel through the calcium sensing receptor (CaSR) in human breast cancer cells

Promkan, Moltira; Patmasiriwat, Pimpicha; Chakrabarty, Subhas

doi:10.1016/j.ceca.2011.01.003

Cited by 33 publications

(31 citation statements)

References 39 publications

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“…It has been reported that extracellular Ca 2+ can down-regulate cell proliferation, invasion and anchorage-independent growth in cancer [25,26]. Recent studies showed that BRCA1 expression could increase the sensitivity of breast cancers to paclitaxel by regulating CaSR [27,28,29]. We investigated the rs17251221 SNP because it is one genetic variation of CaSR.…”

Section: Discussionmentioning

confidence: 99%

A Genetic Polymorphism (rs17251221) in the Calcium-Sensing Receptor is Associated with Breast Cancer Susceptibility and Prognosis

Kong

Jiang

et al. 2014

Cell Physiol Biochem

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Background: Calcium-sensing receptor (CaSR) is a typical G protein coupled receptor. The rs17251221 SNP is located in an intron of the CaSR gene, and the G allele is considered a gain of function mutation. Previous studies revealed that rs17251221 polymorphisms contribute to the risk of developing certain types of cancers. This study investigated the rs17251221 SNP in breast cancer by analyzing the correlation of the rs17251221 genotype with breast cancer susceptibility, clinicopathological features and prognosis. Methods: A TaqMan assay was used to genotype the rs17251221 SNP in a case-control study. The expression levels of CaSR in breast cancer tissues were determined using quantitative reverse-transcription PCR (qRT-PCR) and western blot analysis. The association of the rs17251221 genotype and the clinicopathological characteristics, as well as the prognosis of the breast cancer patient, was assessed statistically. Results: We found that the AG and GG genotypes were associated with lower mRNA and protein levels of CaSR compared to the AA genotype in breast cancer tissues. We also found that the AG and GG genotypes were associated with breast cancer susceptibility, the patient's age at diagnosis, tumor size, lymph node metastasis and estrogen receptor status of breast cancer tissue. More importantly, we found that the genotypes were prognostic markers for both disease-free survival and overall survival of breast cancer. Conclusion: The rs17251221 SNP is a risk factor associated with breast cancer susceptibility, as well as a prognostic indicator. Our data suggest that rs17251221 may be a potential therapeutic target in breast cancer.

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Section: Discussionmentioning

confidence: 99%

A Genetic Polymorphism (rs17251221) in the Calcium-Sensing Receptor is Associated with Breast Cancer Susceptibility and Prognosis

Kong

Jiang

et al. 2014

Cell Physiol Biochem

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“…1.8 and 5.0 mM [8]. In contrast to the above studies suggesting that the CaSR contributes to the aggressiveness of breast cancer cells, the Chakrabarty laboratory had reported that CaSR activation inhibits proliferation and decreases malignant behavior in breast cancer cells [9,10]. Increasing Ca 2? concentrations over this range inhibited proliferation, invasion and anchorage-independent growth of MCF-7, MDA-MB-435 and MDA-MB-231 cells and enhanced sensitivity to cell death in response to paclitaxel, a standard chemotherapeutic drug [9,10].…”

Section: Introductionmentioning

confidence: 92%

“…With the onset of mammary gland involution, CaSR expression again falls to nulliparous levels [6]. CaSR also plays critical roles in the development of mammary cancer [7][8][9][10]. Ahidouch laboratory had reported that elevated Ca 2?…”

Section: Introductionmentioning

confidence: 97%

Parathyroid hormone-related protein overexpression protects goat mammary gland epithelial cells from calcium-sensing receptor activation-induced apoptosis

Sun

Zheng

et al. 2014

Mol Biol Rep

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Normal mammary gland epithelial cells and breast cancer cells express the calcium-sensing receptor (CaSR), which is the master regulator of systemic calcium metabolism. During lactation, activation of the CaSR in mammary epithelial cells downregulates parathyroid hormone-related protein (PTHrP) levels in milk and in the circulation, and increases calcium transport into milk. However, very little information is available on the role of CaSR in goat mammary gland epithelial cells (GMECs) apoptosis. In this investigation, the full-length cDNA of CaSR from Xinong Saanen dairy goats was cloned, which contains an open-reading frame of 3,258 bp encoding 1,085 amino acids with a predicted molecular weight of 121.0 kDa and an isoelectric point of 5.65. The amino acid sequence is highly homologous with sheep, and the goat CaSR gene is mapped to chromosome 1. Quantitative real-time PCR suggested that CaSR was predominantly expressed in the heart, kidney and mammary gland. Then, we found the stimulation of CaSR with its activator gadolinium chloride (GdCl3) contributed to increase CaSR mRNA levels in GMECs and simultaneously promoted cell apoptosis, and these effects were abrogated partially by NPS2390 which is an inhibitor of CaSR. We also demonstrated that Ca(2+) increased CaSR mRNA levels and induced GMECs apoptosis and restrained cell proliferation. In contrast, PTHrP overexpression protected GMECs from calcium-induced apoptosis, and promoted cell proliferation. In conclusion, these results suggest that PTHrP overexpression protects GMECs from CaSR activation-induced apoptosis.

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“…Agonist activation of the CaSR in breast cancer cells downregulates cell proliferation, cell invasion and anchorage-independent growth as well as expression of the anti-apoptotic protein, survivin, and affords an increase in sensitivity to paclitaxel, an important drug used in the treatment of breast cancer (Liu et al, 2009a). Interestingly, the BRCA1 tumour suppressor gene which mimics these effects in breast cancer cells has been shown to do this by regulating the expression of the CaSR and therefore its effect on survivin expression and paclitaxel sensitivity (Promkan et al, 2011).…”

Section: Breast Cancermentioning

confidence: 99%

“…In the lactating breast, expression of the CaSR in mammary epithelial cells can regulate parathyroid hormone-related protein (PTHrP) production and adjust uptake of calcium into milk according to calcium availability (VanHouten et al, 2004). In the normal breast the CaSR has tumour suppressor properties acting in concert with the BRCA1 tumour suppressor to decrease levels of the antiapoptotic protein, survivin, and increase sensitivity to paclitaxel, a drug commonly used in breast cancer treatment (Promkan et al, 2011). However, if expressed in malignant breast cells, the receptor may actually aid bone metastasis (see below under hypercalcaemia of malignancy).…”

Section: +mentioning

confidence: 99%

CASR (Calcium-Sensing Receptor)

Ward¹,

Magno²,

Ratajczak³

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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BRCA1 suppresses the expression of survivin and promotes sensitivity to paclitaxel through the calcium sensing receptor (CaSR) in human breast cancer cells

Cited by 33 publications

References 39 publications

A Genetic Polymorphism (rs17251221) in the Calcium-Sensing Receptor is Associated with Breast Cancer Susceptibility and Prognosis

A Genetic Polymorphism (rs17251221) in the Calcium-Sensing Receptor is Associated with Breast Cancer Susceptibility and Prognosis

Parathyroid hormone-related protein overexpression protects goat mammary gland epithelial cells from calcium-sensing receptor activation-induced apoptosis

CASR (Calcium-Sensing Receptor)

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