A salivary proline-rich peptide of 1932 Da showed a dose-dependent antagonistic effect on the cytosolic Ca2+ mobilization induced by progesterone in a tongue squamous carcinoma cell line. Structure-activity studies showed that the activity of the peptide resides in the Cterminal region characterized by a proline stretch flanked by basic residues. Furthermore, lack of activity of the retro-inverso peptide analogue suggested the involvement of stereospecific recognition. Mass spectrometry-based shotgun analysis, combined with Western blotting tests and biochemical data obtained with the Progesterone Receptor Membrane Component 1 (PGRMC1) inhibitor AG205, showed strong evidence that p1932 performs its modulatory action through an interaction with the progesterone receptor PGRMC1, which is predominantly expressed in this cell line and, clearly, plays a role in progesterone induced Ca2+ response. Thus, our results point to p1932 as a modulator of the transduction signal pathway mediated by this protein and, given a well-established involvement of PGRMC1 in tumorigenesis, highlight a possible therapeutic potential of p1932 for the treatment of oral cancer.

Antagonistic effect of a salivary proline-rich peptide on the cytosolic Ca2+ mobilization induced by progesterone in oral squamous cancer cells

MESSANA, IRENE;CABRAS, TIZIANA;SANNA, MARIA TERESA;
2016

Abstract

A salivary proline-rich peptide of 1932 Da showed a dose-dependent antagonistic effect on the cytosolic Ca2+ mobilization induced by progesterone in a tongue squamous carcinoma cell line. Structure-activity studies showed that the activity of the peptide resides in the Cterminal region characterized by a proline stretch flanked by basic residues. Furthermore, lack of activity of the retro-inverso peptide analogue suggested the involvement of stereospecific recognition. Mass spectrometry-based shotgun analysis, combined with Western blotting tests and biochemical data obtained with the Progesterone Receptor Membrane Component 1 (PGRMC1) inhibitor AG205, showed strong evidence that p1932 performs its modulatory action through an interaction with the progesterone receptor PGRMC1, which is predominantly expressed in this cell line and, clearly, plays a role in progesterone induced Ca2+ response. Thus, our results point to p1932 as a modulator of the transduction signal pathway mediated by this protein and, given a well-established involvement of PGRMC1 in tumorigenesis, highlight a possible therapeutic potential of p1932 for the treatment of oral cancer.
Amino Acid Sequence; Calcium; Carcinoma, Squamous Cell; Cell Line, Tumor; Chromatography, High Pressure Liquid; Cytosol; Humans; Ions; Membrane Proteins; Molecular Sequence Data; Mouth Neoplasms; Peptides; Progesterone; Progestins; Proline-Rich Protein Domains; Protein Binding; Receptors, Progesterone; Salivary Glands; Signal Transduction; Spectrometry, Mass, Electrospray Ionization; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/185843
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