Transcriptomic and proteomic analyses in bone tumor cells: Deciphering parathyroid hormone-related protein regulation of the cell cycle and apoptosis

2012 ◽  
Vol 27 (9) ◽  
pp. 1976-1991 ◽  
Author(s):  
Isabella WY Mak ◽  
Robert E Turcotte ◽  
Michelle Ghert
2005 ◽  
Vol 129 (4) ◽  
pp. 531-533 ◽  
Author(s):  
Lei Chen ◽  
Tri A. Dinh ◽  
Abida Haque

Abstract Small cell carcinoma of the ovary is a rare malignant tumor of the ovary. It is the most common undifferentiated ovarian carcinoma in young women. Approximately two thirds of patients with ovarian small cell carcinoma have hypercalcemia. The mechanism of development of hypercalcemia is unclear, although parathyroid hormone–related protein has been found in some of the cases. Parathormone expression in tumor cells, rarely reported, was seen in this case, suggesting that ectopic parathyroid hormone production by the tumor cells may be the cause of hypercalcemia.


Circulation ◽  
2004 ◽  
Vol 110 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Nathalie Fiaschi-Taesch ◽  
Karen K. Takane ◽  
Sophia Masters ◽  
Juan Carlos Lopez-Talavera ◽  
Andrew F. Stewart

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 861-872 ◽  
Author(s):  
Brian M. Sicari ◽  
Ronnie Troxell ◽  
Fatimah Salim ◽  
Mansoor Tanwir ◽  
Karen K. Takane ◽  
...  

Parathyroid hormone-related protein (PTHrP) contains a classical bipartite nuclear localization signal. Nuclear PTHrP induces proliferation of arterial vascular smooth muscle cells (VSMC). In the arterial wall, PTHrP is markedly up-regulated in response to angioplasty and promotes arterial restenosis. PTHrP overexpression exacerbates arterial restenosis, and knockout of the PTHrP gene results in decreased VSMC proliferation in vivo. In arterial VSMC, expression of the cell cycle inhibitor, p27, rapidly decreases after angioplasty, and replacement of p27 markedly reduces neointima development. We have shown that PTHrP overexpression in VSMC leads to p27 down-regulation, mostly through increased proteosomal degradation. Here, we determined the molecular mechanisms through which PTHrP targets p27 for degradation. S-phase kinase-associated protein 2 (skp2) and c-myc, two critical regulators of p27 expression and stability, and neointima formation were up-regulated in PTHrP overexpression in VSMC. Normalization of skp2 or c-myc using small interfering RNA restores normal cell cycle and p27 expression in PTHrP overexpression in VSMC. These data indicate that skp2 and c-myc mediate p27 loss and proliferation induced by PTHrP. c-myc promoter activity was increased, and c-myc target genes involved in p27 stability were up-regulated in PTHrP overexpression in VSMC. In primary VSMC, PTHrP overexpression led to increased c-myc and decreased p27. Conversely, knockdown of PTHrP in primary VSMC from PTHrPflox/flox mice led to cell cycle arrest, p27 up-regulation, with c-myc and skp2 down-regulation. Collectively, these data describe for the first time the role of PTHrP in the regulation of skp2 and c-myc in VSMC. This novel PTHrP-c-myc-skp2 pathway is a potential target for therapeutic manipulation of the arterial response to injury.


Author(s):  
Jean F. Emly ◽  
Wendy A. Ratcliffe ◽  
Elaine Green ◽  
Sarah J. Bowden ◽  
David A. Heath ◽  
...  

1995 ◽  
Vol 19 (2) ◽  
pp. 292-297 ◽  
Author(s):  
Arnold Tabuenca ◽  
Subburaman Mohan ◽  
Carlos A. Garberoglio ◽  
Patrick I. Borgen ◽  
Thomas Rosol ◽  
...  

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