Calcitonin targets extracellular signal-regulated kinase signaling pathway in human cancers

Abstract

The mitogen-activated protein kinases (MAPKs) signaling pathway is a potential target in cancer therapy. Constitutive phosphorylated extracellular signal-regulated kinase (ERK1/2), which is one of the MAPKs has been detected in a variety of tumors. Calcitonin (CT) is a polypeptide hormone secreted by the thyroid gland and has been used to treat the osteoporosis and humoral hypercalcemia of malignancy. We report that CT decreases ERK1/2 phosphorylation in cancer cells showing constitutive phosphorylated ERK1/2. In MDA-MB-231 cells, a breast cancer cell line showing constitutive phosphorylated ERK1/2, CT phosphorylated c-Raf at Ser 259 via the protein kinase A pathway, resulting in suppression of ERK1/2 phosphorylation. CT significantly reduced the tumor volume of MDA-MB-231 cells showing constitutive phosphorylated ERK1/2 compared with saline buffer. However, CT did not exert any significant effects on the proliferation of MCF-7 cells, a breast cancer cell line, showing non-constitutive phosphorylated ERK1/2. These novel findings indicate that CT may be used to target ERK in the treatment of cancer.

Cancer and Hypercalcemia; a Review of the Diagnosis and Treatment Through an Unusual Case

“…Therefore, we administered calcitonin via subcutaneous route unfortunately without any decrease in serum calcium levels. Glucocorticoids at daily doses of 60 mg can be used in cases refractory to hydration, bisphosphonate, and diuretic therapy (27,28). However, our patient did not respond well to glucocorticoid therapy, either.…”

Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells

“…Previously, we demonstrated that CT activation of LLC-PK1 cells stimulated ERK1/2 phosphorylation through MEK (Nakamura et al, 2002), however, CT suppressed ERK1/2 constitutive activation in human cancer cells (Nakamura et al, 2007). We showed that ERK activation by CT is abolished completely by PD98059, however, CTGF expression induced by CT was a partially inhibited by PD98059.…”

Up-regulation of urinary-type plasminogen activator correlates with high-risk papillary thyroid carcinoma with BRAFV600E mutation and its possible molecular mechanism

“…Total RNA was isolated from each cell line and tissue samples using the ULTRASPEC RNA Isolation System (Biotecx, TX) [18]. cDNA was synthesized using the SuperScript First-Strand Synthesis System for RT-PCR (Invitrogen, CA).…”

“…The PCR reaction primers for uPA and BRAF were as follows: uPA forward 5 -AAGGACTACAGCG-CTGACAC-3 , reverse 5 -AACTCCTGCAGGCTTCAGTC-3 ; BRAF forward 5 -GCACAGGGCATGGATTACTT-3 , reverse 5 -GATGACTTC-TGGTGCCATCC-3 . RT-PCR analysis with ˇ-actin primers was used as an internal quality control [18]. In addition, the purified PCR products of cDNA for the BRAF gene (exon 15) were sequenced using PCR primers as previously described [15].…”