Fibroblast growth factor 8 increases breast cancer cell growth by promoting cell cycle progression and by protecting against cell death.

Summary, in English

Fibroblast growth factor 8 (FGF-8) is expressed in a large proportion of breast cancers, whereas its level in normal mammary gland epithelium is low. Previous studies have shown that FGF-8b stimulates breast cancer cell growth in vitro and in vivo. To explore the mechanisms by which FGF-8b promotes growth, we studied its effects on cell cycle regulatory proteins and signalling pathways in mouse S115 and human MCF-7 breast cancer cells. We also studied the effect of FGF-8b on cell survival. FGF-8b induced cell cycle progression and up-regulated particularly cyclin D1 mRNA and protein in S115 cells. Silencing cyclin D1 with siRNA inhibited most but not all FGF-8b-induced proliferation. Inhibition of the FGF-8b-activated ERK/MAPK pathway decreased FGF-8b-stimulated proliferation. Blocking the constitutively active PI3K/Akt and p38 MAPK pathways also lowered FGF-8b-induced cyclin D1 expression and proliferation. Corresponding results were obtained in MCF-7 cells. In S115 and MCF-7 mouse tumours, FGF-8b increased cyclin D1 and Ki67 levels. Moreover, FGF-8b opposed staurosporine-induced S115 cell death which effect was blocked by inhibiting the PI3K/Akt pathway but not the ERK/MAPK pathway. In conclusion, our results suggest that FGF-8b increases breast cancer cell growth both by stimulating cell cycle progression and by protecting against cell death.

• Författare: Emeli Nilsson; Leon Brokken; Pirkko Härkönen
• Avdelning/ar: Institutionen för translationell medicin
• Publiceringsår: 2010
• Språk: Engelska
• Sidor: 800-812
• Publikation/Tidskrift/Serie: Experimental Cell Research
• Volym: 316
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/19962979?dopt=Abstract; http://dx.doi.org/10.1016/j.yexcr.2009.11.019
• Dokumenttyp: Artikel i tidskrift
• Förlag: Academic Press
• Ämne: Cancer and Oncology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1090-2422