Mid-region parathyroid hormone-related protein (PTHrP) and gene expression of MDA-MB231 breast cancer cells.

Rosalia Sirchia, Claudio Luparello

Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Palermo, Italy. clupar@tin.it

Biological chemistry 2007 May

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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, for which tumorigenesis was also attenuated in vivo. We have also demonstrated that mid-region PTHrP gains access to the nuclear compartment of these cells and displays DNA-binding properties in vitro by recognizing targets in both cellular chromatin and isolated oligonucleotides. Here, we examined whether PTHrP(38-94) amide was able to modulate gene expression of MDA-MB231 cells, employing a combination of conventional, differential display and semi-quantitative multiplex PCR techniques. The results obtained provide first evidence that PTHrP(38-94) amide can affect gene expression in tumor cells, identifying A4-differentiation protein/PLP2 as up-regulated, and HOX7/MSX1, COX6C, FZD6, OXR1 and TMCO4 as down-regulated genes in treated cells, and suggest that the cytotoxic activity of the peptide can be ascribed, at least in part, to such transcriptional reprogramming.

Citation

Rosalia Sirchia, Claudio Luparello. Mid-region parathyroid hormone-related protein (PTHrP) and gene expression of MDA-MB231 breast cancer cells. Biological chemistry. 2007 May;388(5):457-65