Interleukin-24 Induces Expression of β4 Integrin but Suppresses Anchorage-Independent Growth of Rat Mammary Tumor Cells by a Mechanism That Is Independent of β4
| Autor: | Michael C. Archer, Yaacov Ben-David, You-Jun Li, Wanli Xuan, Guodong Liu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
STAT3 Transcription Factor
Cancer Research Gene Expression Mice Nude Rats Inbred WF Apoptosis Cell Growth Processes Adenocarcinoma Mice Cell Movement In vivo Cell Line Tumor Interleukin 24 Animals STAT3 Molecular Biology Mammary tumor biology Microarray analysis techniques Interleukins Integrin beta4 Mammary Neoplasms Experimental Microarray Analysis Rats Up-Regulation Oncology Cell culture Cancer research biology.protein Ectopic expression Anchorage-Independent Growth Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Molecular Cancer Research. 7:433-442 |
| ISSN: | 1557-3125 1541-7786 |
| DOI: | 10.1158/1541-7786.mcr-08-0252 |
| Popis: | Wistar-Furth rats develop multiple mammary adenocarcinomas following initiation with methylnitrosourea, whereas Copenhagen rats are resistant to the development of mammary tumors. We have previously isolated cell lines from tumors induced in resistant Copenhagen × Wistar-Furth F1 rats by infusion of a retrovirus harboring v-Ha-ras directly into the main mammary ducts. Some of the cell lines were able to grow in soft agar, but a significant number did not display anchorage-independent growth. Here, we compared by microarray analysis genes that are differentially expressed in these cell lines. The expression of interleukin-24 (IL-24) and β4 integrin was highly correlated with the inability of cells to grow in soft agar. Ectopic expression of IL-24 in anchorage-independent cells inhibited their growth in monolayer culture, in soft agar, and in nude mice in vivo and inhibited their ability to migrate and invade in in vitro assays. Furthermore, growth suppression by IL-24 was associated with the transcriptional up-regulation of p27Kip1 via the activation of Stat3. We showed, for the first time, that β4 integrin is a downstream target of IL-24. However, β4 does not play a direct role in regulating the proliferative capacity of rat mammary tumor cells. Our results show that IL-24 suppresses the growth of rat mammary carcinoma cells and may play a role in the resistance of Copenhagen rats to mammary carcinogenesis. (Mol Cancer Res 2009;7(3):433–42) |
| Databáze: | OpenAIRE |
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