scholarly journals Inhibitory effects of 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid on parathyroid hormone-related protein expression by oral cancer cells (HSC-3)

1998 ◽  
Vol 156 (2) ◽  
pp. 349-357 ◽  
Author(s):  
M Abe ◽  
N Akeno ◽  
S Ohida ◽  
N Horiuchi
Keyword(s):  
Retinoic Acid ◽  
Parathyroid Hormone ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Related Protein ◽  
Dihydroxyvitamin D3 ◽  
Serum Free ◽  
1,25 Dihydroxyvitamin D3 ◽  
Parathyroid Hormone Related Protein ◽  
Serum Free Conditions

We investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 9-cis-retinoic acid (9cRA) on parathyroid hormone-related protein (PTHrP) production and its mRNA expression by the human oral squamous carcinoma cell line (HSC-3). The major transcript of PTHrP was 1.5 kb in human HSC-3 cells. In the presence and absence of serum, 1,25(OH)2D3 produced dose-dependent inhibition of PTHrP gene expression and secretion. Significant inhibition by 1,25(OH)2D3 in the presence of serum was observed at 10(-10) M for mRNA expression and 10(-8) M for secretion, whereas under serum-free conditions, 1,25(OH)2D3 significantly suppressed PTHrP mRNA expression at 10(-10) M and secretion at 10(-9) M. Thus the remainder of the experiments were performed under serum-free conditions. After 24 h of incubation, 9cRA decreased dose-dependently PTHrP mRNA expression and PTHrP secretion. Addition of 10(-7) M 1,25(OH)2D3 or 10(-7) M 9cRA to HSC-3 cells significantly suppressed PTHrp transcription within 1 h and the PTHrP secretion within 12 h. Maximal suppression of mRNA expression was maintained for 12-48 h. 9cRA caused a continuous decrease in PTHrP secretion for up to 48 h, whereas the inhibition of secretion by 1,25(OH)2D3 was transient and abolished by 48 h. Neither 1,25(OH)2D3 nor 9cRA altered the stability of PTHrP mRNA. The inhibitory effect of 1,25(OH)2D3 and 9cRA on PTHrP mRNA expression was additive, whereas no additive effect was observed with regard to PTHrP secretion. These results indicate that 1,25(OH)2D3 and 9cRA suppressed PTHrP production and mRNA expression in oral squamous cancer cells, and suggest that transcriptional suppression may act through binding of the heterodimer (vitamin D receptor-retinoid X receptor) to negatively responsive elements of the PTHrP gene.

scholarly journals Parathyroid Hormone-related Protein Regulates Tumor-relevant Genes in Breast Cancer Cells

2006 ◽  
Vol 281 (21) ◽  
pp. 14563-14572 ◽  
Author(s):  
Angela Dittmer ◽  
Martina Vetter ◽  
Dario Schunke ◽  
Paul N. Span ◽  
Fred Sweep ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone-related protein ameliorates death receptor-mediated apoptosis in lung cancer cells

2003 ◽  
Vol 285 (6) ◽  
pp. C1429-C1436 ◽  
Author(s):  
Randolph H. Hastings ◽  
Flavio Araiza ◽  
Douglas W. Burton ◽  
Lu Zhang ◽  
Maxwell Bedley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Parathyroid Hormone ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Cancer Progression ◽  
Caspase 3 ◽  
Death Receptor ◽  
Related Protein ◽  
Caspase 9 ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone-related protein (PTHrP) is expressed in more advanced, aggressive tumors and may play an active role in cancer progression. This study investigated the effects of PTHrP on apoptosis after UV irradiation, Fas ligation, or staurosporine treatment in BEN human squamous lung carcinoma cells. Cells at 70% confluency were treated for 24 h with 100 nM PTHrP-(1-34), PTHrP-(38-64), PTHrP-(67-86), PTHrP-(107-139), or PTHrP-(140-173) in media with serum, exposed for 30 min to UV-B radiation (0.9 mJ/cm2), and maintained for another 24 h. Caspase-3, caspase-8, and caspase-9 activities increased fivefold. Pretreatment with PTHrP-(1-34) and PTHrP-(140-173) ameliorated apoptosis after UV irradiation, as indicated by reduced caspase activities, increased cell protein, decreased nuclear condensation, and increased clonal survival. Other peptides had no effect on measures of apoptosis. PTHrP-(140-173) also reduced caspase activities after Fas ligation by activating antibody, but neither peptide had effects on caspase-3 or caspase-9 activity after 1 μM staurosporine. These data indicate that PTHrP-(1-34) and PTHrP-(140-173) protect against death receptor-induced apoptosis in BEN lung cancer cells but are ineffective against mitochondrial pathways. PTHrP contributes to lung cancer cell survival in culture and could promote cancer progression in vivo. The mechanism for the protective effect against apoptosis remains to be determined.

scholarly journals Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

2005 ◽  
Vol 12 (3) ◽  
pp. 549-583 ◽  
Author(s):  
G A Clines ◽  
T A Guise
Keyword(s):  
Parathyroid Hormone ◽  
Bone Metastases ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Major Public Health Problem ◽  
Related Protein ◽  
Vicious Cycle ◽  
Parathyroid Hormone Related Protein ◽  
Osteolytic Bone Disease

Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the ‘seed and soil’ hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-β that further stimulates local cancer cells. This ‘vicious cycle’ of bone metastases represents reciprocal bone/cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the ‘vicious cycle’ is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.

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