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

Fabio Caradonna, Claudio Luparello, Giulia Sciandrello, Isabel López De Silanes, Nieves Olmo, Javier Turnay, M. Antonia Lizarbe, Andrew F. Stewart, Giuseppa Barbata, Rosalia Sirchia

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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".
Original languageEnglish
Pages (from-to)105-116
Number of pages12
JournalBreast Cancer Research and Treatment
Volume105
Publication statusPublished - 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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