Regulation of PTHrP and PTH/PTHrP Receptor by Extracellular Ca2+Concentration and Hormones in the Breast Cancer Cell Line 8701-BC

Luparello, Claudio; Santamaria, Francesca; Schilling, Tobias

doi:10.1515/bc.2000.039

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…[12][13][14][15][16] Potential PTH1R transcripts have been detected in breast tissue and in breast cancer cell lines. [17][18][19] PTH-1-34 and PTHrP-1-34 have shown strong evidence for the existence of two distinct regions in the N-terminal and C-terminal domains, and the interaction between the N-and C-terminal domains of PTH-1-34 and PTHrP-1-34 have been reflected in the very weak binding of PTH-15-34 and PTHrP-1-14. 20,21 There is evidence that the PTHrP N-terminal region can sterically hinder receptor binding if certain side chains are modified.…”

Section: Introductionmentioning

confidence: 99%

Quantitative comparison of PTH1R in breast cancer MCF7 and osteosarcoma SaOS‐2 cell lines

Alokail

Peddie

2008

Cell Biochemistry & Function

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The aim of the present study was to compare the classical parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptors in MCF7 breast cancer cells with SaOS-2 osteosarcoma cell line. Quantitative binding showed that (125)I-PTHrP-1-34(Tyr) binds with a single binding site in both cells. However (125)I-PTHrP-1-34(Tyr) has higher affinity binding in MCF7 (K(D) = 1.88 +/- 0.08 nM) than in SaOS-2 cells (K(D) = 4.4 +/- 0.185 nM). The competitive binding using 3.3 nM (125)I-PTHrP-1-34(Tyr) with increasing amounts (0.33-33 nM) of unlabelled human PTHrP-1-34, PTHrP-7-34, PTHrP-1-86 His(5)-PTHrP-1-36, His(5)-Phe(23)-PTHrP-1-36 or PTH-1-34 revealed different displacements. In SaOS-2 the PTHrP-7-34 and PTHrP-1-86 caused similar displacement compared with 73% by PTH-1-34 and 70% by PTHrP-1-34. However, in MCF7, PTHrP-7-34, PTHrP-1-86 and PTH-1-34 displaced by 54%, 72% and 67%, respectively, compared to 87% by PTHrP-1-34. The His(5)-Phe(23)-PTHrP-1-36 caused an increase in the K(D) from 2.0 +/- 0.03 nM to 2.75 +/- 0.045 nM in MCF7 cells, but had no significant effect in SaOS-2 cells. The PTH/PTHrP receptor in both cell lines revealed a single 85 KDa band with different intensity. Our results suggest that the PTH/PTHrP receptor in MCF7 cells has higher binding affinity for PTHrP than PTH compared to the receptor in SaOS-2 cells.

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Section: Introductionmentioning

confidence: 99%

Quantitative comparison of PTH1R in breast cancer MCF7 and osteosarcoma SaOS‐2 cell lines

Alokail

Peddie

2008

Cell Biochemistry & Function

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“…Breast cancer was one of the original tumors from which PTHrP was purified and sequenced [17], and it is now known that it is a key factor controlling bone homing and resorption by metastasizing breast cells [2]. Some of us have reported that PTHrP expression by neoplastic breast cells ''in vitro'' is drastically modulated by modifications of the culture microenvironment [18,19]; in addition, data have been produced demonstrating that different PTHrP domains are also biologically-active on breast tumour cells in culture [20][21][22]. In particular, PTHrP (38-94)-amide, administered at 1 nM concentration was found able to restrain growth and invasion as well as to cause striking toxicity and accelerate death of a panel of breast cancer cell lines, the most responsive being MDA-MB231.…”

Section: Introductionmentioning

confidence: 99%

Midregion PTHrP regulates Rip1 and caspase expression in MDA-MB231 breast cancer cells

Luparello

Sirchia

Sasso

2007

Breast Cancer Res Treat

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It was previously reported that the midregion PTHrP domain (38-94)-amide restrains growth and invasion "in vitro", causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231 whose tumorigenesis was also attenuated "in vivo". In addition, we have demonstrated that midregion PTHrP is imported in the nucleoplasm of cultured MDA-MB231 cells, and that "in vitro" it can bind chromatin of metaphase spread preparations and also an isolated 20-mer oligonucleotide, thereby appearing endowed with a putative transcription factor-like DNA-binding ability. Here, we examined whether PTHrP (38-94)-amide was able to modulate the expression of genes encoding for apoptosis factors and caspases. Employing a combination of conventional and semi-quantitative multiplex PCR techniques, antisense oligonucleotide (asODN) transfections, proliferation/invasion assays and protein analyses, here we report that PTHrP treatment induces the up-regulation of Bcl-xS, Bad and Rip1 and switches-on the expression of caspase-2, -5, -6, -7 and -8 in MDA-MB231 cells. Moreover, we demonstrate for the first time that asODN-induced under-expression of Rip1 can lead to a more pronounced up-regulation of some caspases due, at least in part, to JNK inactivation, thus providing a new example of factor involved in the transcriptional regulation of the apoptotic enzymes.

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“…Guise et al [17] have shown that PTHrP is a key factor implicated in both the osteotropism of breast cancer metastases, and in breast cancer-mediated bone resorption. Using ''in vitro'' systems, we have demonstrated that PTHrP expression by breast cancer cells can be drastically modulated by modifications of the ''in vitro'' microenvironment [18,19], and that non-N terminal PTHrP domains may exert an effect on the biological behaviour of diverse tumour cell lines [11,12,20,21]. In particular, the midregion PTHrP domain, i.e.…”

Section: Introductionmentioning

confidence: 99%

Mid-region parathyroid hormone-related protein (PTHrP) binds chromatin of MDA-MB231 breast cancer cells and isolated oligonucleotides “in vitro”

Sirchia

Priulla

Sciandrello

et al. 2006

Breast Cancer Res Treat

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We have previously shown that PTHrP(38-94)-amide restrains growth and invasion "in vitro", causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231 whose tumorigenesis was also attenuated "in vivo". PTHrP(38-94)-amide contains the domain implicated in the nuclear import of PTHrP. Although the nucleus was identified as a destination for mid-region PTHrP, evidence for direct DNA-binding capability is lacking to date. Here, we examined the localization of PTHrP(38-94)-amide within MDA-MB231 cells and within metaphase spread preparations and characterized its DNA-binding properties, employing a combination of immunocytochemical, cytogenetic, "whole genome"/conventional PCR, EMSA and DNase footprinting techniques. The results obtained: (i) show that PTHrP(38-94)-amide gains access to the nuclear compartment of MDA-MB231 cell; (ii) demonstrate that PTHrP(38-94)-amide is a DNA-binding peptide; and, (iii) represent the first data to date on the potential molecular targets in both cellular chromatin and isolated oligonucleotides "in vitro".

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Regulation of PTHrP and PTH/PTHrP Receptor by Extracellular Ca2+Concentration and Hormones in the Breast Cancer Cell Line 8701-BC

Cited by 16 publications

References 34 publications

Quantitative comparison of PTH1R in breast cancer MCF7 and osteosarcoma SaOS‐2 cell lines

Quantitative comparison of PTH1R in breast cancer MCF7 and osteosarcoma SaOS‐2 cell lines

Midregion PTHrP regulates Rip1 and caspase expression in MDA-MB231 breast cancer cells

Mid-region parathyroid hormone-related protein (PTHrP) binds chromatin of MDA-MB231 breast cancer cells and isolated oligonucleotides “in vitro”

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