Calcitonin is a prostate epithelium-derived growth stimulatory peptide

Chien, Jeremy; Ren, Yuan; Wang, Yong Qing; Bordelon, William; Thompson, Evelin; Davis, Robert J.; Rayford, Walter; Shah, Girish V.

doi:10.1016/s0303-7207(01)00530-5

Cited by 38 publications

(107 citation statements)

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“…*p < 0.05; **p < 0.001 (one-way ANOVA and Newman-Keul's test). tently secrete several-fold greater amounts of CT, 18,30 we attempted to simulate this phenomenon by upregulating or downregulating CT expression in PC-3M cells using appropriate expression constructs. The results have demonstrated that the upregulation of CT expression in PC-3M cells led to a marked increase in the secretion of uPA activity.…”

Section: Discussionmentioning

confidence: 99%

“…18 The cloned cDNA was inserted into mammalian expression vector pcDNA3.1 (Research Genetics) in sense direction. The sense orientation of the insert in the cloned plasmid was confirmed by sequencing at the institutional DNA sequencing facility.…”

Section: Plasmids and Generation Of Pc-3m Variant Cell Linesmentioning

confidence: 99%

“…Considering that tumor cells of primary PCs secrete CT and uPA and their amounts may vary with their tumor grade, 18 we modulated endogenous CT expression of PC-3M cells by stably transfecting either constitutively active CT vector (PC-3M-CT1) or anti-CT ribozyme (PC-3M-CT2) as described recently. 38 The controls for these 2 cell lines expressed either the empty vector pcDNA3.1 (PC-3M-v) or inactive ribozyme (R4).…”

Section: Modulation Of Ct Expression In Pc-3m Cells Alters Upa Secretionmentioning

confidence: 99%

“…[13][14][15][16][17] Previous studies from this laboratory have shown that CT and its receptors are expressed in primary prostate tumors, and the level of their expression positively correlates with tumor grade. 18 CT and CT receptors (CTRs) have also been identified in several established PC cell lines such as LNCaP, PC-3, DU-145 and PC-3M. [19][20][21][22] Exogenously added CT stimulates the proliferation of LNCaP cells by stimulating cAMP accumulation and increasing cytoplasmic Ca 21 transients, and stimulates invasion by activating protein kinase A-mediated mechanisms.…”

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Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

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Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several folds higher than that in benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation increases invasiveness of prostate cancer (PC) cells via activation of protein kinase A. Since the role of urokinase-type plasminogen activator (uPA) in invasion of PC has been established, we tested the hypothesis that CT increases invasion of PC cells by stimulating uPA secretion from PC cells. Exogenously added CT stimulated the secretion of uPA from PC-3M cells in a dose-dependent manner, which was blocked by Rp.cAMP, a competitive inhibitor of protein kinase A. CT stimulated the secretion of MMP-2 and MMP-9 from PC-3M cells, and also increased their invasiveness. Both these actions of CT were blocked by uPA-neutralizing antibodies. Immunofluorescence studies with PC-3M cells suggest that CT stimulated redistribution of cellular uPA to focal adhesion sites, which was further confirmed by co-immunoprecipitation of uPA with focal adhesion kinase (FAK) in response to CT. These results suggest that CT increases invasiveness of PC cells by stimulating PKA-mediated uPA secretion and by redirecting the secreted uPA to focal adhesion sites. The results also suggest that uPA may, at least in part, mediate proinvasive actions of CT on PC cells by stimulating the secretion of gelatinases and degradation of focal adhesion sites. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Plasmids and Generation Of Pc-3m Variant Cell Linesmentioning

confidence: 99%

Section: Modulation Of Ct Expression In Pc-3m Cells Alters Upa Secretionmentioning

confidence: 99%

mentioning

confidence: 99%

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Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

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“…Currently, CT is a therapeutic agent for treatment of bone diseases such as osteoporosis and Paget's disease [10,16]. Expression of CT in tissue from the brain, prostate and uterus has been reported [3][4][5], and this suggests that it has additional functions other than those for osteoclasts and the kidney. As supporting evidence for additional functions, the CT expression levels have been shown to be related with tumorigenicity of prostate cancer [15] and to be increased in the pregnant rat uterus during implantation [4].…”

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confidence: 99%

Expression Profile and Localization of Mouse Calcitonin (CT) Sense/Antisense Transcripts in Pre- and Postnatal Tissue Development

Rezaeian

Nishibori

Hiraiwa

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. Calcitonin (CT) has been shown to have various functions including osteoclast activity and calcium and phosphorus metabolism in mammals. In the present study, we measured the amounts of CT mRNA in the mouse brain, liver, kidney, heart and testis at various development stages, 14 days post-coitum (dpc), 17-dpc, newborn, 1 week and 8 weeks (adult), using real-time PCR. In the brain and kidney, the amount of CT mRNA decreased with development. In the testis, elevated amounts were observed at 17-dpc and 8 weeks. In the liver, the amount increased from the 14 dpc embryo to newborn stage and then decreased. In the heart, elevated amounts were observed at 17-dpc. Additionally, the CT antisense transcript was determined using a modified RT-PCR and nucleotide sequencing in the present study. Organs with high mRNA expressions were examined for localization of transcripts using in situ hybridization. The CT sense and antisense transcripts in the 14 dpc brain were mainly localized in the mesencephalon. In the pre-and postnatal stages, sense and antisense transcripts were shown to exist rather uniformly in the kidney, heart, liver and testis. In the 17-dpc rib and thyroid lobe and the adult ovary, the sense and antisense transcripts were found to be densely localized. KEY WORDS: calcitonin, in situ hybridization, mouse, sense/antisense transcripts.J. Vet. Med. Sci. 71 (5): [561][562][563][564][565][566][567][568] 2009 Calcitonin (CT) is a 32 amino acid peptide hormone that has been shown to participate in osteoclast activity and reabsorption of calcium and phosphorus through target organ comprised of the bone and kidney in mammals. CT is mainly produced in parafollicular cells (C cells) in the thyroid gland and is produced in a wide variety of other tissues [12]. Currently, CT is a therapeutic agent for treatment of bone diseases such as osteoporosis and Paget's disease [10,16]. Expression of CT in tissue from the brain, prostate and uterus has been reported [3][4][5], and this suggests that it has additional functions other than those for osteoclasts and the kidney. As supporting evidence for additional functions, the CT expression levels have been shown to be related with tumorigenicity of prostate cancer [15] and to be increased in the pregnant rat uterus during implantation [4]. Furthermore, treatment with antisense olignucleotide of CT mRNA severely impairs embryo implantation [18].In the past several years, the number of sense and antisense pair transcripts reported has sharply increased [7]. Due to the increase in the number of these studies, researchers have initiated investigations of not only of the localization of antisense transcripts but also of regulation of sense transcripts with their antisense transcripts in order to more fully understand the molecular interaction occurring in individual loci, cells and tissues. Changes in the expression levels of each non-coding RNA have been described for complex diseases such as cancer [1,14,17] and neurological diseases [11].However, little is known about th...

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Calcitonin increases invasiveness of prostate cancer cells: Role for cyclic AMP-dependent protein kinase A in calcitonin action

et al. 2005

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Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several-fold higher than from benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation stimulates growth of prostate cancer (PC) cells via activation of adenylyl cyclase and calcium/phospholipid pathways. To identify the role of ''CT System'' in prostate cancer, we tested the expression of CT and CTR mRNAs in invading tumor cells of prostate cancer specimens. The effect of CT on in vitro invasion of PC cell lines and on activation of gelatinases was also examined. The cells of primary tumors and those invading stroma co-expressed CT/CTR mRNAs. Exogenously added CT increased in vitro invasion of PC cell lines and caused a rapid, several-fold but transient increase in protein kinase A activity. In contrast, anti-CT serum caused a dose-dependent inhibition of in vitro invasion of PC-3M cells. CT also increased the concentration and activities of MMP-2 and MMP-9. Rp.cAMP, a competitive inhibitor of cAMP-dependent protein kinase A, myristoylated protein kinase A inhibitory peptide (PKI) as well as the expression of dominant negative form of PKA all attenuated basal in vitro invasion of PC-3M cells, and CT could not increase in vitro invasiveness in their presence. These results suggest that overexpression of ''CT System'' in invasive PC tumors significantly contributes to increased invasiveness of prostate cancer cells. The action of CT may be mediated by protein kinase A signaling, which subsequently leads to increased cell invasion and secretion of gelatinases. ' 2005 Wiley-Liss, Inc.Key words: prostate cancer; invasion; calcitonin; PKA; metastasis Calcitonin (CT), a 32 amino acid peptide produced by C cells of mammalian thyroid, has also been detected in human brain, the pituitary gland, lung carcinoma as well as the conditioned media from the cultures of primary prostate epithelial cells.1-6 Although most well-known functions of CT include inhibition of bone resorption, renal regulation of sodium, phosphate, calcium and neuromodulation, 6 CT has also been shown to regulate secretory and proliferative functions of several organs. [7][8][9] Previous studies from this laboratory have shown that immunoreactive CT (iCT) is secreted by primary prostate epithelial cells, and its secretion from cancer-derived primary prostate cells is several-fold higher than that from the cells of benign prostatic hyperplasia origin. 1 We have reported that mRNAs for CT and its receptor (CTR) are selectively localized to the basal epithelium of benign prostates but are distributed throughout the epithelium of malignant prostates. High-affinity CT receptors have been identified in membrane preparations of primary tumors as well as androgen-responsive LNCaP and highly metastatic but androgen refractory PC-3M prostate cancer cells.10 Exogenously added CT stimulates the proliferation of LNCaP cells by stimulating cAMP accumulation and increasing cytoplasmic Ca 21 transients, and CT al...

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Calcitonin is a prostate epithelium-derived growth stimulatory peptide

Cited by 38 publications

References 20 publications

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Expression Profile and Localization of Mouse Calcitonin (CT) Sense/Antisense Transcripts in Pre- and Postnatal Tissue Development

Calcitonin increases invasiveness of prostate cancer cells: Role for cyclic AMP-dependent protein kinase A in calcitonin action

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