Studies on mice may reveal why some are more suspectible to carcinogens...
 

http://www.liverandpancreas.com/lab/

Interesting studies are being done on why organ injury and carcingens can be more potent in some mice with MIC-1 depletion.Also, GDF 14/15 may regulate parenchymal cell proliferation after tissue injury and the cytokine inflammatory response. Such studies give interesting ideas why some individuals may get cancer when others don't.

more on MIC macrophage inhibitory cytokine and Breast cancer
 

The macrophage inhibitory cytokine integrates AKT/PKB and MAP kinase signaling pathways in breast cancer cells

Wyatt Wollmann 1, Mike L. Goodman 1, Poornima Bhat-Nakshatri 4, 5, Hiromitsu Kishimoto 1, Robert J. Goulet, Jr 1, Sanjana Mehrotra 3, Akira Morimiya 3, Sunil Badve 3 and Harikrishna Nakshatri 1, 2, 4, 5, * 1 Department of Surgery, 2 Department of Biochemistry and Molecular Biology, 3 Department of Pathology and 4 Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA and 5 Walther Cancer Institute, Indianapolis, IN 46208, USA

* To whom correspondence should be addressed at: R4-202 Indiana Cancer Research Institute, 1044 West Walnut Street, Indianapolis, IN 46202, USA. Tel: +1 317 278 2238; Fax: +1 317 274 0396; Email: hnakshat@iupui.edu



Macrophage inhibitory cytokine 1 (MIC-1), a divergent member of the transforming growth factor beta superfamily, plays a role in the progression of a number of cancers, including breast, gastric, prostate and colorectal carcinomas. Serum MIC-1 levels are elevated in patients with metastatic prostate, breast and colorectal carcinomas. In vitro studies have revealed a cell type-specific role for MIC-1 in senescence and apoptosis. MIC-1 activates the survival kinase AKT/PKB in neuronal cells. Depending on the cell type, it activates or represses the MAP kinases ERK1/2. Mechanisms responsible for an increased MIC-1 expression in cancers and the consequences of MIC-1 overexpression, however, are not known. In this study, we show that AKT/PKB directly regulates the expression of MIC-1 in breast cancer cells. Sequences within –88 to +30 of the MIC-1 promoter are required for the AKT-mediated induction of MIC-1. This region of the promoter contains two SP-1 binding sites (SP-1B and SP-1C), which bind to the SP-1 and SP-3 proteins. Mutation of SP-1C but not SP-1B reduced the AKT-mediated activation of MIC-1. MIC-1 increased the basal ERK1 phosphorylation and prolonged the estrogen-stimulated ERK1 phosphorylation in MCF-7 breast cancer cells without altering the phosphorylation status of AKT/PKB. Immunohistochemistry with MIC-1 antibody revealed an MIC-1 expression within the cancer cells of primary breast cancer and in the MCF-7 xenografts. Furthermore, a limited analysis of RNA from primary breast cancers revealed an overexpression of MIC-1 in tumors, compared with normal tissues. These results suggest that AKT/PKB through MIC-1 could regulate the ERK1 activity and the MIC-1 expression levels may serve as a surrogate marker for the AKT activation in tumors.



Abbreviations: CA-AKT, constitutively active AKT; EMSA, electrophoretic mobility shift assay; ERhttp://carcin.oxfordjournals.org/math/alpha.gif, estrogen receptor alpha; KD-AKT, kinase dead AKT; MIC-1, macrophage inhibitory cytokine 1; RT–PCR, reverse transcription–polymerase chain reaction

complete article at http://carcin.oxfordjournals.org/cgi.../full/26/5/900