Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site

Foley, John; Wysolmerski, John J.; Missero, Caterina; King, Connie S.; Philbrick, William M.

doi:10.1016/s0303-7207(99)00151-3

Cited by 15 publications

(12 citation statements)

References 52 publications

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“…Our results are in accordance with previous studies that measured alternative promoter usage in various cell lines and in lung carcinoma (16,17 ). Furthermore, several reports on the regulation of individual promoters in different cancers have identified some of the transcription factors regulating PTHrP expression and have highlighted the importance of the P3 promoter in gene transactivation (20,(22)(23)(24)(25). The results given in previous reports analyzing the prevalence of all three isoforms in healthy and neoplastic tissues by use of nonquantitative RT-PCR or Northern blots are comparable to our results.…”

supporting

confidence: 92%

Quantitative Evaluation of Alternative Promoter Usage and 3′ Splice Variants for Parathyroid Hormone-related Protein by Real-Time Reverse Transcription-PCR

Richard¹,

Luchin²,

Brena

et al. 2003

Clinical Chemistry

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supporting

confidence: 92%

Quantitative Evaluation of Alternative Promoter Usage and 3′ Splice Variants for Parathyroid Hormone-related Protein by Real-Time Reverse Transcription-PCR

Richard¹,

Luchin²,

Brena

et al. 2003

Clinical Chemistry

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“…Activation of Ets-1 occurs via Ras-mitogen activated protein kinase (MAPK) signaling involving Mek-1 and Erk-1/2 kinases. Activated Ets-1 was shown to transactivate PTHrP using an Ets-binding site in P3 in breast cancer cells, [38][39][40] murine keratinocytes 41 and HTLV-1-infected cells. 30 We have previously reported that severe combined immunodeficient (SCID)/beige (bg) mice inoculated with ATLL cells develop solid lymphoma and HHM characterized by severe hypercalcemia, increased osteoclastic bone resorption, decreased bone mineral density and increased circulating PTHrP that correlated positively with plasma calcium concentrations.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma

et al. 2005

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Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy seen in the majority of adult T-cell leukemia/lymphoma (ATLL) patients with human T-cell lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 Tax has been shown to complex with ETS-1 and SP1 to transactivate the PTHrP P3 promoter. Previously, we established a SCID/bg mouse model of human ATL with RV-ATL cells and showed that PTHrP expression was independent of Tax. In this study, we report an inverse correlation of PTHrP with tax/rex mRNA in multiple HTLV-1-positive cell lines and RV-ATL cells. Stimulation of Jurkat T cells with PMA/ionomycin upregulated the PTHrP P3 promoter by a previously characterized Ets binding site and also induced protein/DNA complex formation identical to that observed in RV-ATL cells. Further, we provide evidence that cotransfection with Ets-1 and constitutively active Mek-1 in HTLV-1-negative transformed T cells with stimulation by PMA/ionomycin not only resulted in a robust induction of PTHrP P3 but also formed a complex with ETS-1/P3 EBS similar to that in ATLL cells. Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner.

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“…been identified [18][19][20], which contribute to the regulation of the promoter by transforming growth factor β (TGFβ), human Tcell lymphotrophic virus I-transactivator of the X region (HTLV-I-Tax), retinoic acid and adenovirus early region 1A protein [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Ets2 and protein kinase Cepsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells

Lindemann

Braig

Hauser

et al. 2003

Biochemical Journal

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Parathyroid hormone-related protein (PTHrP) promotes the metastatic potential and proliferation of breast cancer cells, and acts anti-apoptotically. In invasive MDA-MB-231 breast cancer cells, transforming growth factor β-regulated PTHrP synthesis is mediated by an Ets1/Smad3-dependent activation of the PTHrP P3 promoter. In the present study, we studied the regulation of PTHrP expression in non-invasive, Ets1-deficient and transforming growth factor β-resistant MCF-7 cells. We found PMA to be a strong stimulator of P3-dependent PTHrP expression in MCF-7 cells. Mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase 1 (MEK-1)/ERK1/2 inhibitor PD98059 interfered with this activity. Promoter studies revealed that the PMA effect depended on the Ets and stimulating protein-1 (Sp1)-binding sites. Of several Ets factors tested, Ets2, but not Ese-1, Elf-1 or Ets1, supported the PMA-dependent increase in promoter activity. PD98059 and a threonine to alanine mutation of the ERK1/2-responsive Ets2 phosphorylation site at position 72 inhibited the Ets2/PMA effect. Activated protein kinase C (PKC)ε could mimic PMA by stimulating the P3 promoter alone or in co-operation with Ets2 in an MEK-1/ERK1/2-dependent manner. Activated PKCα, although capable of co-operating with Ets2, failed to induce transcription from the P3 promoter on its own. The Ets2/PKCα synergistic effect was neither sensitive to PD98059 nor to Thr 72 /Ala 72 mutation. PMA neither increased the expression of Sp1 nor modulated the transcriptional activity of Sp1. However, it induced the displacement of a yet unknown factor from the Sp1-binding site, which may result in Sp1 recruitment to the promoter. Our results suggest an ERK1/2-dependent Ets2/PKCε synergism to be involved in PTHrP expression in MCF-7 breast cancer cells.

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Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site

Cited by 15 publications

References 52 publications

Quantitative Evaluation of Alternative Promoter Usage and 3′ Splice Variants for Parathyroid Hormone-related Protein by Real-Time Reverse Transcription-PCR

Quantitative Evaluation of Alternative Promoter Usage and 3′ Splice Variants for Parathyroid Hormone-related Protein by Real-Time Reverse Transcription-PCR

Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma

Ets2 and protein kinase Cepsilon are important regulators of parathyroid hormone-related protein expression in MCF-7 breast cancer cells

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