Words similar to pthrp
Example sentences for: pthrp
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PTHrP Exon 2 forward 5' AGGAGGCGGTTAGCCCTG 3'
Evidence has been accumulated that TGFβ promotes late-stage tumorigenesis by stimulating angiogenesis and invasive behaviour of tumor cells, enhancing immunosuppression and supporting epithelial-mesenchymal transition of cancer cells [ 4 ] . Furthermore, TGFβ is believed to be part of a vicious circle in bone metastases as it gets released from osteoclast-degraded bone substance and subsequently stimulates PTHrP gene expression in nearby metastatic cancer cells which in turn leads to an activation of osteoclastic bone resorption [ 11 ] . Therefore, it is of great interest to understand in more detail the molecular aspects of TGFβ-mediated gene expression in metastatic breast cancer cells and to explore ways to interfere with this tumorigenic signalling.
The smad7 gene contains a perfect palindromic Smad binding element (GTCTAGAC) while the pai-1 and the pthrp promoters harbor AGAC tandem repeats [ 19 33 ] which binds Smad proteins less efficiently [ 34 ] . The upa gene contains only an AP1-binding site which resembles the Smad3/4-responsive AGAC motif [ 35 ] . A weaker binding site could require Smad3 to be present at higher concentrations for efficient binding and would make TGFβ-dependent transcription from a gene more vulnerable to reduced nuclear accumulation of the Smad3 protein.
Fast TGFβ responder genes, such as smad7 , whose maximum activation by TGFβ was reached after 60 min, was only slightly affected by SB-203580, while slow responders, such as pai-1, pthrp or upa , that showed peak activation after 180-240 min, were very sensitive to the repressive effect of SB-203580.
Furthermore, our previous work has shown that, in invasive breast cancer cells, Ets proteins activate the PTHrP P3 promoter in cooperation with Smad3 [ 19 ] . In this context it is interesting to note that TGFβ signalling seemed to target the ets-1 and ets-2 gene (Fig.
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