Autocrine loops

Protection appears to be mediated by PKC activation. Radiation induces b-EGE production by these cells, allowing a survival-associated positive autocrine loop to develop. 

Chen Y, Thai P, Zhao YH, Ho YS, DeSouza MM, Wu R Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop. J Biol Chem 2003 278 17036-17043. 

Figure 5.8. Several cells secreting IL-6 also display IL-6 receptors on their surface, thus facilitating autocrine regulation by this interleukin. In the case of fibroblasts and endothelial cells, this regulation appears negative (inhibitory to cell growth). In the case of plasmacytoma cells, however, the autocrine loop is positive, with IL-1 stimulating further growth...

Fig. 14.3. Autocrine loops in tumor formation. Due to an error in control of transcription, growth factors may be produced and secreted in the cell which wonld normally only be formed in low concentrations or not at all. If the cell also possesses the receptors corresponding to the growth factor, the growth factor can then bind and activate a mitogenic signal chain. In this situation, the cell creates the mitogenic signal itself There is evidence that the growth factors can become active intracellularly. The mechanism behind this is nnknown.

Fig. 1. Proposed mechanism of action of rituximab associated with the apoptosis pathway. Binding of rituximab with the CD20 antigen up-regulates the production of interleukin-10 (IL-10). The IL-10 autocrine loop down-regulates the expression of the bcl-2 protein, which inhibits the intrinsic pathway (or mitochondrial mediated pathway) of apoptosis. The mitochondrial pathway is induced by intracellular stress signals. The translocation of the bcl-2 protein into the mitochondria leads to the activation of caspase 9 via release of cytochrome c and apoptotic protease-activating factor 1. The other pathway, the extrinsic pathway (or death receptor mediated pathway) activates caspase 8. Subsequently, caspase 8 or 9 activates caspase 3, leading to programmed cell death (apoptosis).

Bergquist J, Tarkowski A, Ekman R, Ewing A (1994) Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop. Proc. Natl. Acad. Sci. U SA 91 12912-12916. 

C17. Connolly, J. M., and Rose, D. P, Regulation of DU-145 human prostate cancer cell by insulin-like growth factors and its interaction with the epidermal growth factor autocrine loop. 

Browder, T. M., Dunbar, C. E. and Nienhuis, A. W. (1990). Private and public autocrine loops in neoplastic cells. Cancer Cells 1, 9-17. 

CSF, M-CSF, called the autocrine loop). TNF-a and IL-1 are potent upregulators of several cell t) es including fibroblasts and T cells. TNF-a may act earlier in the hierenchy than other cytokines and has proven to be an important target for anticytokine therapy in rheumatoid arthritis and Crohn s disease (see later, anti-TNF therapy). Some small amounts of anti-inflammatory cytokines may also be present (such as IL-10 and interferon-y), but because the system is not in balance, the end result is inflammation. 

TGFp blocks the growth-promoting effects of cytokines such as EGF, PDGF, and the FGFs, and many malignant cells both produce and respond to it. A negative autocrine loop... 

Oscillatory release of GnRH could also rely on an autocrine loop involving negative (Bourguignon et al, 1994) or positive (Krsmanovic et al, 1993) feedback. The possibility of positive feedback in GnRH secretion is suggested by the presence of GnRH receptors on the surface of... 

DoUe L., El Yazidi-Belkoura I., Adriaenssens E., Nurcombe V., Hondermarck H., (2003), Nerve growth factor overexpression and autocrine loop in breast cancer cells. Oncogens 22 5592-601. 

Marin y Montero-Julian FA, Gres S, Boulay V, Bongrand P, Farnarier C, Kaplanski G The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation An experimental model involving thrombin. J Iimnunol 2001 167 3435. 

There are two major ways that c-kit mediates rapid cell growth in SCLC (1) throngh the c-kit/SCF autocrine loop and (2) throngh the overexpression with increased... 

Bellusci, S. et al, Creation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity. 

---