Effects of transforming growth factor β1 on cell growth and parathyroid hormone-related protein in Walker 256 tumor cells

Benitez-Verguizas, J; Loarte, D.; Miguel, F.; Esbrit, Pedro

doi:10.1016/s0024-3205(99)00437-3

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…Previous studies have reported that the half-life of PTHrP mRNA (all transcripts) ranges from 30 min to more than 3 h, depending on the cell type (Heath et al 1995, Werkmeister et al 1998, Benitez-Verguizas et al 1999. Based on our studies, it is likely that the wide range of PTHrP mRNA half-lives (all transcripts) reported in the literature was due to differences in isoform expression.…”

supporting

confidence: 57%

“…In addition, the increased PTHrP mRNA expression associated with these cytokines has been demonstrated to be due, in part, to the stabilization of PTHrP mRNA (Heath et al 1995, Benitez-Verguizas et al 1999, Sellers et al 2002. Studies have demonstrated that each of the PTHrP mRNA isoforms has a variable half-life that is differentially altered by cytokine treatment.…”

Section: Introductionmentioning

confidence: 99%

“…For example, it has been reported that EGF increased the half-life of PTHrP 139 mRNA, but not PTHrP 141 or 173 mRNA (Heath et al 1995). Although there are reports of the effect of TGF-1 on PTHrP mRNA transcription and stability (Heath et al 1995, Benitez-Verguizas et al 1999, regulation of PTHrP mRNA stability and steady-state levels of specific isoforms of PTHrP mRNA by TGF-1 have not been extensively examined. In cancer, changes in the cellular PTHrP mRNA expression profile, through differences in the cytokine milieu or alterations in cell function, may contribute to the development of HHM or the rate of tumor metastasis (Guise et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability

Sellers

Luchin²,

Richard³

et al. 2004

Journal of Molecular Endocrinology

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supporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability

Sellers

Luchin²,

Richard³

et al. 2004

Journal of Molecular Endocrinology

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“…TGF␤ has the potential to affect both PTHrP transcription and stability of PTHrP RNA (15)(16)(17)(18). To assess the contribution of RNA stabilization to the effect of TGF␤ on PTHrP expression in MDA-MB-231 cells, we inhibited transcription by actinomycin D. We found that actinomycin D substantially inhibited up-regulation of the PTHrP P3-specific transcript by TGF␤ (Fig.…”

Section: Tgf␤1 Induces Pthrp Expression Primarily Through the P3mentioning

confidence: 91%

“…Such a TGF␤/ PTHrP feedback loop is thought to significantly contribute to the progression of breast metastases in bone (14). TGF␤ stimulates PTHrP expression in a variety of cell lines by increasing the PTHrP mRNA level (15)(16)(17)(18). Of the three promoters (P1-P3) that can drive PTHrP transcription in humans, the proximal P3 promoter (formerly called P2 promoter) is always active in PTHrP-expressing breast tumors (19).…”

mentioning

confidence: 99%

Transforming Growth Factor β Regulates Parathyroid Hormone-related Protein Expression in MDA-MB-231 Breast Cancer Cells through a Novel Smad/Ets Synergism

Lindemann

Ballschmieter

Nordheim

et al. 2001

Journal of Biological Chemistry

111

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The majority of breast cancers metastasizing to bone secrete parathyroid hormone-related protein (PTHrP). PTHrP induces local osteolysis that leads to activation of bone matrix-borne transforming growth factor ␤ (TGF␤). In turn, TGF␤ stimulates PTHrP expression and, thereby, accelerates bone destruction. We studied the mechanism by which TGF␤ activates PTHrP in invasive MDA-MB-231 breast cancer cells. We demonstrate that TGF␤1 up-regulates specifically the level of PTHrP P3 promoter-derived RNA in an actinomycin D-sensitive fashion. Transient transfection studies revealed that TGF␤1 and its effector Smad3 are able to activate the P3 promoter. This effect depended upon an AGAC box and a previously described Ets binding site. Addition of Ets1 greatly enhanced the Smad3/TGF␤-mediated activation. Ets2 had also some effect, whereas other Ets proteins, Elf-1, Ese-1, and Erf-1, failed to cooperate with Smad3. In comparison, Ets1 did not increase Smad3/TGF␤-induced stimulation of the TGF␤-responsive plasminogen activator inhibitor 1 (PAI-1) promoter. Smad3 and Smad4 were able to specifically interact with the PTHrP P3-AGAC box and to bind to the P3 promoter together with Ets1. Inhibition of endogenous Ets1 expression by calphostin C abrogated TGF␤-induced up-regulation of the P3 transcript, whereas it did not affect the TGF␤ effect on PAI expression. In TGF␤ receptor II-and Ets1-deficient, noninvasive MCF-7 breast cancer cells, TGF␤1 neither influenced endogenous PTHrP expression nor stimulated the PTHrP P3 promoter. These data suggest that TGF␤ activates PTHrP expression by specifically up-regulating transcription from the PTHrP P3 promoter through a novel Smad3/Ets1 synergism.Parathyroid hormone-related protein (PTHrP)

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Parathyroid hormone-related protein and ezrin are up-regulated in human lung cancer bone metastases

Deng,

Tannehill-Gregg,

Nadella

et al. 2007

Clin Exp Metastasis

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Lung cancer often metastasizes to bone in patients with advanced disease. Identification of the factors involved in the interactions between lung cancer cells and bone will improve the prevention and treatment of bone metastases. We identified changes in metastasis-related gene expression of human HARA lung squamous carcinoma cells co-cultured with neonatal mouse calvariae using a pathway-specific microarray analysis. Nine genes were up-regulated and two genes down-regulated in HARA cells co-cultured with mouse calvariae. Five of the nine up-regulated genes, including caveolin 1, CD44, EphB2, ezrin, and Parathyroid hormone-related protein (PTHrP), and one down-regulated gene, SLPI, were further confirmed by Reverse transcription-polymerase chain reaction (RT-PCR). A mouse model was subsequently used to study the role of PTHrP and ezrin in bone metastasis in vivo. PTHrP (all three isoforms) and ezrin were up-regulated in HARA cells at sites of bone metastasis as detected by RT-PCR and immunohistochemistry. The PTHrP 141 mRNA isoform was increased by the greatest extent (13.9-fold) in bone metastases compared to PTHrP 139 and PTHrP 173 mRNA. We then generated a HARA cell line in which PTHrP expression was inducibly silenced by RNA interference. Silencing of PTHrP expression caused significant reduction of submembranous F-actin and decreased HARA cell invasion. Ezrin up-regulation was confirmed by Western blots on HARA cells co-cultured with adult mouse long bones. Further, Transforming growth factor beta (TGF-beta) was identified as one of the factors in the bone microenvironment that was responsible for the up-regulation of ezrin. The identification of PTHrP and ezrin as important regulators of lung cancer bone metastasis offers new mechanistic insights into the metastasis of lung cancer and provides potential targets for the prevention and treatment of lung cancer metastasis.

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Effects of transforming growth factor β1 on cell growth and parathyroid hormone-related protein in Walker 256 tumor cells

Cited by 14 publications

References 26 publications

Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability

Alternative splicing of parathyroid hormone-related protein mRNA: expression and stability

Transforming Growth Factor β Regulates Parathyroid Hormone-related Protein Expression in MDA-MB-231 Breast Cancer Cells through a Novel Smad/Ets Synergism

Parathyroid hormone-related protein and ezrin are up-regulated in human lung cancer bone metastases

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