Modulation of cyclin D1 expression in human tumoral parathyroid cells: effects of growth factors and calcium sensing receptor activation.
The study investigated cyclin D1 regulation by growth factors and calcium sensing receptor (CaSR) in human tumoral parathyroid cells. Basic fibroblast and epidermal growth factors increased cyclin D1 and phosphorylated extracellular signal-regulated kinases (pERK1/2) levels that were both efficiently inhibited by CaSR agonists. By contrast, in growth factors-free medium cyclin D1 levels were either unaffected or stimulated by CaSR activation independently from ERK1/2 pathway. Transforming growth factor beta (TGFbeta) reduced cyclin D1 levels in the majority of tumors, this effect being not influenced by CaSR activation and menin expression levels. In conclusion, in parathyroid tumors cyclin D1 expression was modulated by growth factors and CaSR activation. These data further support the oncogenic role of cyclin D1, which resulted to be target for stimulation by bFGF and EGF and inhibition by CaSR and TGFbeta signalling in the parathyroid.
Corbetta
S
S
Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, Policlinico SDonato IRCCS, Via Morandi 30, 20097, SDonato Mse (MI), Italy. sabrina.corbetta@unimi.it
Eller-Vainicher
C
C
Vicentini
L
L
Lania
A
A
Mantovani
G
G
Beck-Peccoz
P
P
Spada
A
A
D019938:Cyclin D1 / Q000096:biosynthesis* / Q000378:metabolism; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D010280:Parathyroid Glands / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D044169:Receptors, Calcium-Sensing; D018168:Receptors, Retinoic Acid; D016212:Transforming Growth Factor beta; C082925:retinoic acid receptor beta; D019938:Cyclin D1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3