title: Midregion parathyroid hormone-related protein inhibits growth and invasion in vitro and tumorigenesis in vivo of human breast cancer cells.
abstract: Parathyroid hormone-related protein (PTHrP) is critical for normal mammary development and is overexpressed by breast cancers. PTHrP is a peptide hormone that undergoes extensive post-translational processing, and PTHrP(38-94)-amide is one of the mature secretory forms of the peptide. In this study, we explored the effect of PTHrP(38-94)-amide in a panel of six breast cancer cell lines "in vitro" and in MDA-MB231 cells "in vivo" specifically examining cell viability, proliferation, invasiveness, and growth in nude mice. PTHrP(38-94)-amide markedly inhibited proliferation and also caused striking toxicity and accelerated cell death in breast cancer cells. In addition, direct injection of PTHrP(38-94)-amide into MDA-MB231 breast cancer cells passaged in immunodeficient mice produced a marked reduction in tumor growth. These studies (i) indicate breast cancer cells are one of the few tissues in which specific effects of midregion PTHrP have been established to date, (ii) support a role for midregion secretory forms of PTHrP in modulating not only normal but also pathological mammary growth and differentiation, (iii) add further evidence for the existence of a specific midregion PTHrP receptor, and (iv) provide a novel molecule for modeling of small molecule analogues that may have anti-breast cancer effects.
authors.affiliation: Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Luparello
authors.forename: R
authors.initials: R
authors.lastname: Romanotto
authors.forename: A
authors.initials: A
authors.lastname: Tipa
authors.forename: R
authors.initials: R
authors.lastname: Sirchia
authors.forename: N
authors.initials: N
authors.lastname: Olmo
authors.forename: I
authors.initials: I
authors.lastname: López de Silanes
authors.forename: J
authors.initials: J
authors.lastname: Turnay
authors.forename: M A
authors.initials: MA
authors.lastname: Lizarbe
authors.forename: A F
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins