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Carcinogenesis 7: Tumor Promotion and Signaling

LRP12 participates in the TGF- β signaling pathway in human fibrosarcoma cell line SHAC

Jie Zhang, Veronica M. Maher and J. Justin McCormick
Jie Zhang
Michigan State University, East Lansing, MI
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Veronica M. Maher
Michigan State University, East Lansing, MI
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J. Justin McCormick
Michigan State University, East Lansing, MI
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DOI:  Published May 2005
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Proc Amer Assoc Cancer Res, Volume 46, 2005

Abstract

3930

Low Density Lipoprotein Receptor-Related Protein 12 (LRP12) is a newly identified member of the LRP family. It is expressed in normal fibroblasts, but only at very low levels in human fibrosarcoma cells. A previous study in this laboratory suggested that the cytoplasmic tail of LRP12 interacts with several signaling proteins, including a truncated form of the SMAD Anchor for Receptor Activation (SARA). SARA is a protein in the TGF-β signaling pathway. To determine whether LRP12 formed a complex with SARA, we co-transfected LRP12 and full-length SARA DNA into 293 cells. These proteins co-immunoprecipitated, indicating complex formation. When we treated SHAC fibrosarcoma cells expressing LRP12 with TGFβ1 (2.5ng/ml), we found that Smad2 exhibited increased phosphorylation level than the vector controls. SHAC cells treated with TGFβ1 also expressed higher levels of Plasminogen Activator Inhibitor type 1 (PAI-1) protein in the cells and in the culture medium than the control cells when assayed by Western Blotting and ELISA. It is known that TGF-β signaling pathway can cross-talk with the MAPK pathway. Our results also showed that expression of LRP12 could enhance the TGFβ-induced activation of Erk/JNK/p38 kinases of the MAPK pathway. These data suggest that reduced expression of LRP12 in SHAC cells may lead to aberrant TGF-β signaling, which can be expected to play a role in the malignant transformation of these cells. (Supported by NIH CA98305 to JJM).

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Cancer Research: 65 (9 Supplement)
May 2005
Volume 65, Issue 9 Supplement
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LRP12 participates in the TGF- β signaling pathway in human fibrosarcoma cell line SHAC
Jie Zhang, Veronica M. Maher and J. Justin McCormick
Cancer Res May 1 2005 (65) (9 Supplement) 925;

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LRP12 participates in the TGF- β signaling pathway in human fibrosarcoma cell line SHAC
Jie Zhang, Veronica M. Maher and J. Justin McCormick
Cancer Res May 1 2005 (65) (9 Supplement) 925;
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