Change in gene expression profile induced by alpha-melanocyte stimulating hormone in a malignant mesothelioma cell line.
We have previously reported that the peptide a-melanocyte stimulating hormone (alpha-MSH) has antiproliferative effects in human malignant mesothelioma cells. To determine the molecular mechanisms underlying such effects, we investigated the changes in gene expression profile induced by the alpha-MSH analog [Nle4 -DPhe7 ]-alpha-MSH (NDP-alpha-MSH) in a human malignant mesothelioma cell line. The cDNA macroarray technique revealed changes in expression of genes involved in cell growth, adhesion, signal transduction, and transcription. In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer. Further, NDP-alpha-MSH exerted a favorable transcriptional regulation of certain integrins and their signaling pathways. Finally, peptide treatment was associated with a prominent inhibition of IL-13, a cytokine with tumor-promoting effects. The data indicate that the influences of alpha-MSH extend beyond the established anti-inflammatory effects in normal cells to include cell cycle regulatory properties in malignant cells.
Colombo
G
G
Center for Preclinical Investigation, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via F. Sforza 35, Milano 20122, Italy.
Sordi
A
A
Turcatti
F
F
Carlin
A
A
Rossi
C
C
Lonati
C
C
Santambrogio
L
L
Gatti
S
S
Catania
A
A
D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019925:Cyclin A / Q000235:genetics; D056751:Cyclin A2; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology*
C503721:CCNA2 protein, human; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056751:Cyclin A2; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D018793:Interleukin-13; C064352:MYBL2 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-