Advertisement

Analysis of Androgen-Induced Increase in Lipid Accumulation in Prostate Cancer Cells

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 776)

Abstract

Increased metabolic activity is a hallmark of proliferating cancer cells. One common deregulated metabolic pathway in prostate cancer is de novo lipogenesis which is highly increased in prostate cancer and is linked to poor prognosis and metastasis. Male sex hormones play an essential role in prostate cancer growth and have been shown to increase the expression and activity of several lipogenic factors, such as fatty acid synthase (FASN) and sterol regulatory element-binding proteins (SREBPs), leading to accumulation of neutral lipids in prostate cancer cells. These factors are being evaluated as potential prognostic markers and therapeutic targets in prostate cancer. Here we describe methods to directly detect and quantify accumulation of neutral lipids and assess concomitant changes in lipogenic gene expression in LNCaP prostate cancer cells.

Key words

Prostate cancer de novo lipogenesis neutral lipids Oil red O confocal microscopy spectrophotometric analysis 

Notes

Acknowledgments

This work was supported by grants from the Norwegian Cancer Society and the Norwegian Research Council.

References

  1. 1.
    Flavin, R., Peluso, S., Nguyen, P. L., and Loda, M. (2010) Fatty acid synthase as a potential therapeutic target in cancer, Future Oncol 6, 551–562.PubMedCrossRefGoogle Scholar
  2. 2.
    Menendez, J. A., and Lupu, R. (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis, Nat Rev Cancer 7, 763–777.PubMedCrossRefGoogle Scholar
  3. 3.
    Swinnen, J. V., Roskams, T., Joniau, S., Van Poppel, H., Oyen, R., Baert, L., Heyns, W., and Verhoeven, G. (2002) Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer, Int J Cancer 98, 19–22.PubMedCrossRefGoogle Scholar
  4. 4.
    Rossi, S., Graner, E., Febbo, P., Weinstein, L., Bhattacharya, N., Onody, T., Bubley, G., Balk, S., and Loda, M. (2003) Fatty acid synthase expression defines distinct molecular signatures in prostate cancer, Mol Cancer Res 1, 707–715.PubMedGoogle Scholar
  5. 5.
    Swinnen, J. V., Heemers, H., van de Sande, T., de Schrijver, E., Brusselmans, K., Heyns, W., and Verhoeven, G. (2004) Androgens, lipogenesis and prostate cancer, J Steroid Biochem Mol Biol 92, 273–279.PubMedCrossRefGoogle Scholar
  6. 6.
    Zadra, G., Priolo, C., Patnaik, A., and Loda, M. (2010) New strategies in prostate cancer: targeting lipogenic pathways and the energy sensor AMPK, Clin Cancer Res 16, 3322–3328.PubMedCrossRefGoogle Scholar
  7. 7.
    Swinnen, J. V., Esquenet, M., Goossens, K., Heyns, W., and Verhoeven, G. (1997) Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP, Cancer Res 57, 1086–1090.PubMedGoogle Scholar
  8. 8.
    Swinnen, J. V., Van Veldhoven, P. P., Esquenet, M., Heyns, W., and Verhoeven, G. (1996) Androgens markedly stimulate the accumulation of neutral lipids in the human prostatic adenocarcinoma cell line LNCaP, Endocrinology 137, 4468–4474.PubMedCrossRefGoogle Scholar
  9. 9.
    Swinnen, J. V., Ulrix, W., Heyns, W., and Verhoeven, G. (1997) Coordinate regulation of lipogenic gene expression by androgens: evidence for a cascade mechanism involving sterol regulatory element binding proteins, Proc Natl Acad Sci USA 94, 12975–12980.PubMedCrossRefGoogle Scholar
  10. 10.
    Heemers, H., Maes, B., Foufelle, F., Heyns, W., Verhoeven, G., and Swinnen, J. V. (2001) Androgens stimulate lipogenic gene expression in prostate cancer cells by activation of the sterol regulatory element-binding protein cleavage activating protein/sterol regulatory element-binding protein pathway, Mol Endocrinol 15, 1817–1828.PubMedCrossRefGoogle Scholar
  11. 11.
    Heemers, H. V., Verhoeven, G., and Swinnen, J. V. (2006) Androgen activation of the sterol regulatory element-binding protein pathway: Current insights, Mol Endocrinol 20, 2265–2277.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Molecular BiosciencesUniversity of OsloOsloNorway

Personalised recommendations