Mid-region parathyroid hormone-related protein (PTHrP) and gene expression of MDA-MB231 breast cancer cells.
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.
Sirchia
Rosalia
R
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Palermo, Italy. clupar@tin.it
Luparello
Claudio
C
D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D044162:Parathyroid Hormone-Related Protein