Abstract | BACKGROUND: METHODS: Series of lower and higher passages of LNCaP cell sublines were generated by a long-term exposure of LNCaP cells in IL-6-containing culture media. The characteristics of these cell sublines were analyzed and the potential roles of neuroendocrine (NE) differentiation and androgen receptor (AR) activation were examined. RESULTS: We demonstrated that while short-term treatment of IL-6 inhibits LNCaP cell growth by a paracrine mechanism associated with NE differentiation, long-term treatment of IL-6 promotes LNCaP cell growth by an autocrine mechanism accompanied by an activation of AR signaling. In the lower passages (less than 28 passages) of LNCaP cells treated with IL-6, the cell growth was severely retarded which is associated with NE-like morphology and increased expression of NE markers such as neuronspecific enolase (NSE) and chromgranin A (ChgA), and loss of AR expression. However, in the higher passages (higher than 42 passages) of LNCaP cells treated with IL-6, cells started to express endogenous IL-6. At the same time, NE characteristics were disappeared, AR signaling was activated and cells growth was accelerated. Knocking down the AR activation of the higher passages of LNCaP cells abolished autocrine IL-6-induced growth stimulation. CONCLUSIONS: These studies suggest that acquisition of endogenous IL-6 production after prolong exposure of prostate cancer cells to IL-6 may contribute to an autocrine cell growth stimulation. Furthermore, the transition of IL-6 from a paracrine growth inhibitor to an autocrine growth stimulator suggests that IL-6 plays an important role during prostate cancer progression, possibly androgen-independent progression.
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Authors | Soo Ok Lee, Jae Yeon Chun, Nagalakshmi Nadiminty, Wei Lou, Allen C Gao |
Journal | The Prostate
(Prostate)
Vol. 67
Issue 7
Pg. 764-73
(May 15 2007)
ISSN: 0270-4137 [Print] United States |
PMID | 17373716
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2007 Wiley-Liss, Inc. |
Chemical References |
- Chromogranin A
- Growth Inhibitors
- Growth Substances
- Interleukin-6
- Receptors, Androgen
- Phosphopyruvate Hydratase
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Topics |
- Cell Line, Tumor
- Cell Transformation, Neoplastic
(genetics, pathology)
- Chromogranin A
(genetics, physiology)
- Disease Progression
- Gene Expression Regulation, Neoplastic
(drug effects)
- Growth Inhibitors
(genetics, physiology)
- Growth Substances
(genetics, physiology)
- Humans
- Interleukin-6
(genetics, pharmacology, physiology)
- Male
- Neurosecretory Systems
(pathology)
- Phosphopyruvate Hydratase
(genetics, physiology)
- Prostatic Neoplasms
(genetics, pathology, physiopathology)
- Receptors, Androgen
(genetics, physiology)
- Signal Transduction
(physiology)
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