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

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Abstract

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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Acknowledgments

This work was supported by a grant from the University of Palermo (R.S. ex 60%). We thank Prof. A.F. Stewart (University of Pittsburgh, USA) for generous gift of purified PTHrP (38–94)-amide and for helpful suggestions.

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  1. Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle Scienze, 90128, Palermo, Italy

    Claudio Luparello, Rosalia Sirchia & Bruna Lo Sasso

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  1. Claudio Luparello
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  2. Rosalia Sirchia
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Correspondence to Claudio Luparello.

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Luparello, C., Sirchia, R. & Lo Sasso, B. Midregion PTHrP regulates Rip1 and caspase expression in MDA-MB231 breast cancer cells. Breast Cancer Res Treat 111, 461–474 (2008). https://doi.org/10.1007/s10549-007-9816-0

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