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Skin Cancer Melanoma PowerPoint Presentation

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Slide 1 - The Effect of Protein kinase C  Association with phospholipase D1 on the growth of human melanoma cells in Superficial Spreading Melanoma. By: Grethel Bibilonia March 14, 2005 Oka, M., T. Kageshita, T. Ono, A. Goto, T. Kuroki, and M. Ichihashi. 2003. Protein kinase C  associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation independent manner in human melanoma cells. The Journal of Investigative Dermatology 121:69-76.
Slide 2 - Introduction What Superficial Spreading Melanoma? What cancer is? How cancer develops? What phospholipase C is? What protein kinase C is? How protein kinase C is activated? Risk factors for melanoma Staging system Treatments
Slide 3 - Superficial Spreading Melanoma (SSM) Copyright 2003 A.D.A.M., Inc. It is the most common and most curable of the skin cancers. It is flat, asymmetrical, unevenly colored, and usually grows outward across the surface of the skin.
Slide 4 - What is Cancer? Is when cells in the body begin to grow out of control. Abnormal cells continue to grow and divide. Abnormal cells outlive normal cells. Metastasis happens as the cancer cells get into the bloodstream.
Slide 5 - How Cancer develops? Cancer cells develop because of damage to DNA. In cancer cells, the DNA is not repaired. Inherit damage DNA. DNA becomes damaged by exposure to something in the environment.
Slide 6 - Melanoma - Overview Is a type of cancer that begins in the melanocytes. Since these cells keep on making melanin, melanoma tumors are often brown or black. It most often appears on the trunk of fair-skinned men and on the lower legs of fair-skinned women. Copyright 2003 A.D.A.M., Inc.
Slide 7 - What is Phospholipase D1 (PLD)? Phospholipase D (PLD) is an enzyme that hydrolyzes phosphatidylcholine to generate a lipid mediator, phosphatic acid. PLD plays a crucial part in the signal transduction of many types of cells, and is activated by protein kinase C  when cells are stimulated. Phosphorylation: addition of a phosphate group, and occurs most commonly by transfer of the phosphate group from ATP to the hydroxyl group of serine, threonine, or tyrosine in the protein.
Slide 8 - What is Protein Kinase C (PKC)? Protein Kinase C (PKC): is a multifunctional protein-serine/threonine kinase that plays an important part in the intracellular signaling of various biologically active substances. It is activated by diacylglycerol (DAG). Protein Kinases: are enzymes that catalyze the phosphorylation of other enzymes. PKC is a family of six or more related enzymes.
Slide 9 - Most members of the PKC family require membrane phospholipids and diacylglycerol (DAG) for activity, and some require calcium as well. PKC is linked with the stimulation of cell growth. The stimulation of cell growth by PKC is probably due to its ability to phosphorylate and activate proteins called MAP kinases.
Slide 10 - How Protein Kinase C (PKC) is Activated? Copyright © 2003 Pearson Education, Inc. 1. When a receptor is activated by the binding of its ligand on the outer surface of the plasma membrane, the receptor-ligand complex associates with the G protein, causing the displacement of GDP by GTP and the dissociation of the GTP-G complex.
Slide 11 - Copyright © 2003 Pearson Education, Inc. 2. The GTP-G complex then binds to phospholipase C, activating it and causing cleavage of PIP2 into one molecule each of Inositol Trisphosphate (InsP3) and diacylglycerol (DAG)
Slide 12 - Copyright © 2003 Pearson Education, Inc. 3. The Inositol Trisphosphate (InsP3) is released into the cytosol, where it triggers the release of calcium. 4. The diacylglycerol (DAG) remains in the membrane where it activates protein kinase C.
Slide 13 - What is the possible involvement of PLD activation in tumor progression in melanoma? Expressions of PLD1 and PKC in primary and metastatic lesions of SSM where examined using immunohistologic techniques, and adenovirus-mediated gene transfer technique. It was demonstrated that basal PLD activity in melanoma cells can be enhanced by PKC through protein-protein interaction in the absence of cell stimulation. Also the elevated basal PLD activity enhances the invasive potential of melanoma cells.
Slide 14 - Materials and Methods 21 primary melanoma lesions were obtained from 12 males and 9 females patients. Seven of the lesions were SSM Patients Stages of Melanoma 1. Four had stage I 2. Eight had stage II 3. Five had stage III 4. Four had stage IV
Slide 15 - Staging – Clark level Level I: In-situ at basement membrane Level II: Through basement membrane into papillary dermis Level III: Spread to papillary/reticular interface Level IV: Spread to reticular dermis Level V: Sub-Cutaneous invasion Copyright  2002 by John Wiley & Sons, Inc.
Slide 16 - Risk Factors for Melanoma Moles Fair skin Family history Immune suppression Genetics UV radiation Age Gender Past History of Melanoma
Slide 17 - Results Both phospholipase D1 (PLD1) and protein kinase C  (PKC) were strongly expressed in primary and metastatic lesions of superficial spreading melanoma (SSM). The results suggest that protein kinase C  associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in melanoma cells.
Slide 18 - Table II. Relationship between the expression of PKC and PLD1 and the thickness of primary SSM lesions Expression of PLD1 and PKC was constantly strong in all stages of SSM lesions. Copyright © 2003 by The Society for Investigative Dermatology, Inc.
Slide 19 - Table III. Summary of the expression of PKC and PLD1 in primary and metastatic lesions of ALM and SSM Expression of PLD1 and PKC was constantly strong in all stages of SSM lesions. Copyright © 2003 by The Society for Investigative Dermatology, Inc.
Slide 20 - Figure 3. Physiologic association of PLD1 with PKC in HM3KO cells. Copyright © 2003 by The Society for Investigative Dermatology, Inc
Slide 21 - Treatments Surgery Chemotherapy Radiation therapy Immunotherapy
Slide 22 - Conclusion The PLD1 protein levels in melanoma cells is higher than in normal melanocytes. High PLD basal activity enhances the in vitro invasive potential of melanoma cells. PLD is involved in the process of tumor cell metastasis, including invasion. Results suggest that PLD is involved in the malignant transformation of cells. PLD and PKC play an important part in tumor cell invasion and metastasis.
Slide 23 - Bibliography Balch C, Buzaid A, Soong S, Atkins M, Cascinelli N, Coit D, Fleming I, Gershenwald J, Houghton A, Kirkwood J, and others. 2001. Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma. Journal of Clinical Oncology 19: 3635-3648. Glanz K, Schoenfeld E, Weinstock M, Layi G, Kidd J, Shigaki D. 2003. Development and reliability of a brief skin cancer risk assessment tool. International Society for Preventive Oncology 27: 311-315. Oka, M., T. Kageshita, A. Goto, T. Kuroki, and M. Ichihashi. 2003. Protein kinase C  associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation independent manner in human melanoma cells. The Journal of Investigative Dermatology 121:69-76. Quinones L, Garcia-Castro I. 2004. Characterization of Human Cell Lines According to their Migratory Properties in Vitro. Society for In Vitro Biology 40: 35-42.
Slide 24 - Bibliography Becker, WM., LJ. Kleinsmith, and J. Hardin. 2003. The World of the Cell. Pearson Education, Inc. 5:1-802. American Cancer Society. What is Melanoma Skin Cancer? January 10, 2005. February 2005. www.cancer.org  American Society for Dermatologic Surgery. January 10, 2005. February 2005. www.asds-net.org  National Cancer Institute. What is Melanoma? January 10, 2005. February 2005. www.cancernet.nci.nih.gov The Skin Cancer Foundation. January 10, 2005. February 2005. www.skincancer.org
 

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