Human Pathology
Volume 41, Issue 4 , Pages 503-512 , April 2010

Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions

  • Clelia Miracco, MD

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • Corresponding Author InformationCorresponding author. Dipartimento di Patologia Umana ed Oncologia Sezione di Anatomia Patologica Università degli Studi di Siena Via delle Scotte 6 53100, Siena, Italy.
    • ,
  • Gabriele Cevenini, MEng

      Affiliations

    • Department of Surgery and Bioengineering, University of Siena, 53100 Siena, Italy
    • ,
  • Alessandro Franchi, MD

      Affiliations

    • Department of Human Pathology and Oncology, University of Florence, Florence, Italy
    • ,
  • Pietro Luzi, MD

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • ,
  • Elena Cosci, BSc

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • ,
  • Vasileios Mourmouras, MD

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • ,
  • Irene Monciatti, BSc

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • ,
  • Susanna Mannucci, BSc

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • ,
  • Maurizio Biagioli, MD

      Affiliations

    • Department of Clinical Medicine and Immunological Science, Section of Dermatology, University of Siena, 53100 Siena, Italy
    • ,
  • Marzia Toscano, MSc

      Affiliations

    • Department of Physiopathology and Experimental Medicine, University of Siena, 53100 Siena, Italy
    • ,
  • Daniele Moretti, PhD

      Affiliations

    • Department of Physiopathology and Experimental Medicine, University of Siena, 53100 Siena, Italy
    • ,
  • Roberto Lio, MD

      Affiliations

    • Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, 53100 Siena, Italy
    • ,
  • Daniela Massi, MD

      Affiliations

    • Department of Human Pathology and Oncology, University of Florence, Florence, Italy

Received 29 June 2009 ,Revised 7 September 2009 ,Accepted 10 September 2009.

References 

  1. Eskelinen EL, Saftig P. Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 1793;2009:664–673
  2. Yu L, Strandberg L, Lenardo MJ. The selectivity of autophagy and its role in cell death and survival. Autophagy. 2008;4:567–573
  3. Chen N, Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta. 2009;
  4. Jin S, White E. Tumor suppression by autophagy through the management of metabolic stress. Autophagy. 2008;4:563–566
  5. Gozuacik D, Kimchi A. Autophagy and cell death. Curr Topics Dev Biol. 2007;78:217–245
  6. Bialik S, Kimchi A. Autophagy and tumor suppression: recent advances in understanding the link between autophagic cell death pathways and tumor development. Adv Exp Med Biol. 2008;615:177–200
  7. Cheong H, Klionsky DJ. Biochemical methods to monitor autophagy-related processes in yeast. Methods Enzymol. 2008;451:1–26
  8. Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. Embo J. 2000;19:5720–5728
  9. Klionsky DJ, Abeliovich H, Agostinis P, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008;4:151–175
  10. Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003;112:1809–1820
  11. Lee JW, Jeong EG, Lee SH, Yoo NJ, Lee SH. Somatic mutations of BECN1, an autophagy-related gene, in human cancers. APMIS. 2007;115:750–756
  12. Marino G, Salvador-Montoliu N, Fueyo A, et al. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J Biol Chem. 2007;282:18573–18583
  13. Ran KM, Kim MS, Oh JE, et al. Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J Pathol. 2008;
  14. Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672–676
  15. Yue Z, Jin V, Yang C, Levine A, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA. 2003;100:15077–15082
  16. Mathew R, Kongara S, Beaudoin B, et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 2007;21:1367–1381
  17. Miracco C, Cosci E, Oliveri G, et al. Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumors. Int J Oncol. 2007;30:429–436
  18. Shen Y, Li DD, Wang LL, Deng R, Zhu XF. Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy. 2008;16:1067–1068
  19. Chen Y, Lu Y, Lu C, Zhang L. Beclin 1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (HIF)-1alpha expression. Pathol Oncol Res. 2009;9:
  20. Pirtoli L, Cevenini G, Tini P, et al. The prognostic role of Beclin 1 protein expression in high-grade gliomas. Autophagy. 2009;5:7
  21. Li BX, Li CY, Peng RQ, et al. The expression of beclin 1 is associated with favorable prognosis in stage IIIB colon cancers. Autophagy. 2009;5:303–306
  22. Shi YH, Ding ZB, Zhou J, Qiu SJ, Fan J. Prognostic significance of Beclin 1–dependent apoptotic activity in hepatocellular carcinoma. Autophagy. 2009;5(3):380–382Epub 2009 Apr 19
  23. Ahn CH, Jeong EG, Lee JW, et al. Expression of beclin 1, an autophagy-related protein, in gastric and colorectal cancers. Apmis. 2007;115:1344–1349
  24. Sato K, Tsuchihra K, Fujii S, et al. Autophagy is activated in colorectal cancer cells and contributes to the tolerance to nutrient deprivation. Cancer Res. 2007;67:9677–9684
  25. Yoshioka A, Miyata H, Doki Y, et al. LC3, an autophagosome marker, is highly expressed in gastrointestinal cancer. Int J Oncol. 2008;33:461–468
  26. Aoki H, Kondo Y, Aldape K, et al. Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy. 2008;4:467–475
  27. Fujii S, Mitsunaga S, Yamazaki M, et al. Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci. 2008;99:1813–1819
  28. de Bruin EC, Medema JP. Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev. 2008;34:737–749
  29. Liang XH, Yu J, Brown K, Levine B. Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function. Cancer Res. 2001;61:3443–3449
  30. Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM. Detection of autophagy in tissue by standard immunohistochemistry: possibilities and limitations. Autophagy. 2006;2:55–57
  31. Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM. In situ detection of starvation-induced autophagy. J Histochem Cytochem. 2006;54:85–96
  32. Degenhardt K, Mathew R, Beaudoin B, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 2006;10:51–64
  33. Satyamoorthy K, Herlyn M. Cellular and molecular biology of human melanoma. Cancer Biol Ther. 2002;1:14–17
  34. Stahl JM, Sharma A, Cheung M, et al. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 2004;64:7002–7010
  35. Sinnberg T, Lasithiotakis K, Niessner H, et al. Inhibition of PI3K-Akt-mTOR signaling sensitizes melanoma cells to cisplatin and temozolomide. J Invest Dermatol. 2009;129:1500–1515
  36. Sharma A, Sharma AK, Madhunapantula SV, et al. Targeting Akt3 signaling in malignant melanoma using isoselenocyanates. Clin Cancer Res. 2009;CCR-08-2214
  37. Mathieu V, Le Mercier M, De Neve N, et al. Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model. J Invest Dermatol. 2007;127:2399–2410
  38. Trinh VA. Current management of metastatic melanoma. AM Health Syst Pharm. 2008;65:S3–S8
  39. Augustine CK, Yoo JS, Potti A, et al. Genomic and molecular profiling predicts response to temozolomide in melanoma. Clin Cancer Res. 2009;15:502–510
  40. Naumann SC, Roos WP, Jöst E, et al. Temozolomide- and fotemustine-induced apoptosis in human malignant melanoma cells: response related to MGMT, MMR, DBSs, and p53. Br J Cancer. 2009;100:322–333
  41. Zheng M, Bocangel D, Ramesh R, et al. Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of 06-methylguanine-DNA-methyltransferase in human melanoma cells. Mol Cancer Ther. 2008;7:3842–3851
  42. Liu B, Cheng Y, Zhang B, et al. Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondria-mediated ROS-p38-p53 pathway. Cancer Lett. 2009;275:54–60
  43. Ganesan AK, Ho H, Bodemann B, et al. Genome-wide-siRNA–based functional genomics of pigmentation identifies novel genes and pathways that impact melanogenesis in human cells. PLoS Genet. 2008;

☆ This study was supported by a grant from the University of Siena (PAR 2005) and from the Italian Ministry of University and Research (PRIN 2004, number 2004062950_003).

PII: S0046-8177(09)00332-3

doi: 10.1016/j.humpath.2009.09.004

Human Pathology
Volume 41, Issue 4 , Pages 503-512 , April 2010

Article Tools

* Image Usage & Resolution