PTHrP promotes homotypic aggregation of breast cancer cells in three-dimensional cultures.
Parathyroid hormone-related protein (PTHrP) regulates growth and migration of adherent breast cancer cells. Here, we show that PTHrP also interferes with the ability of breast cancer cells to aggregate in suspension cultures. Cell colonies were significantly smaller when the expression of PTHrP or its target genes, integrin alpha6 or KISS-1, was suppressed by RNA interference. TGFbeta1, a stimulator of PTHrP transcription, abolished the effect of PTHrP and KISS-1 specific siRNAs and increased ERK1/2 phosphorylation, whereas inhibition of ERK1/2 phosphorylation by U0126 reduced colony size. PTHrP and KISS-1 may regulate colony formation in 3D by influencing ERK1/2 phosphorylation.
Klinik für Gynäkologie, Universität Halle, Halle, Saale, Germany.
Angela
A
Dittmer
Dario
D
Schunke
Jürgen
J
Dittmer
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002070:Butadienes / Q000494:pharmacology; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D059648:Kisspeptins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D002070:Butadienes; D039503:Integrin alpha6; C106628:KISS1 protein, human; D059648:Kisspeptins; D009570:Nitriles; D044162:Parathyroid Hormone-Related Protein; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3