Cell differentiation and Cancer cells Cell differentiation Cell differentiation occurs in multicellular organisms 2. Why a fertilized egg can develop into different cells: Gene differentiated express 4. House-keeping genes and luxury genes 5. Transdifferentiation: From one type of cell into another type Cell totipotency ( 细胞全能性) 1. Plant cells 2. Animal cloning—Stem cell and its differentiation potential 1. What is a stem cell ? 2. Where to get the stem cells? 3. Types of stem cells: differentiation potential 4.Why do researchers study stem cells ? 5. Stem cell plasticity Cancer:   Cells proliferate uncontrollably 1. The biology characteristics of cancer 2. The causes of cancer 3. Caner: As a result of the accumulation of  mutation and natural selection (1) Proto-oncogens: Gain-of-function mutations (2) Tumor suppressor genes:  Loss-of-function mutations "Remember, you are only an expert from things done in the past. There are no experts from things that will happen in the future."  Dr. Folkman (5) Lose Contact inhibition in vitro Carcinogenic chemicals and UV DNA and RNA tumor viruses Alter the genome SV40, Adenovirus HIV Benign tumor Malignant tumor Normal cell Cancer-inducing mutation genes Proto-oncogenes Tumor-suppressor genes  癌基因（oncogenes ）：v-onc and c-onc  抑癌基因（tumor-suppressor gene ）Rb p53  特点原癌基因抑癌基因基因属性细胞增殖必需细胞分化必需致癌方式基因突变激活、异常表达基因缺失或失活Rous(1910) 发现鸡的致癌RNA 病毒；1963 年发现RSV 突变株：tsRSV 鸡成纤维细胞40C 37C 细胞正常病毒正常繁殖细胞癌变病毒正常繁殖tdRSV  鸡成纤维细胞40C 37C 细胞正常细胞正常病毒正常繁殖病毒正常繁殖v-oncogene tdRSV3’端缺失1500 －2000bp; 不影响病毒复制，但影响细胞转化1976 年发现，正常鸡细胞核DNA 中，具有与V-onc 的同源序列，称正常细胞中的同源序列为原癌基因（protooncogene ）,或C-oncogene. v-onc 和c-onc 的关系：c-onc 来自v-onc.  理由如下: 1 、v-onc 对病毒复制和生存都是不必要的；而c-onc 对细胞重要功能和活动不可缺少；提示c-onc 是进化中保存下来的细胞重要结构元件。2 、发现的30 种c-onc 是依靠病毒的v-onc 探针找到的；并不是所有c-onc 都有对应的同源v-onc 。3 、v-src 缺失3/4 不能致癌的RSV, 注入鸡体内，发现缺失的v-src 与c-src 发生重组，v-src 回复并致癌。抑癌基因（tumor suppressor gene ）Harris(1968): 癌细胞系与同组织正常细胞融合杂交细胞无恶性表型，也不致癌；随着染色体丢失则可能恢复致癌（Rb—13q14.1 ）. Proto-oncogenes Ras oncogene:  Retain bind GTP Bcl-2 oncogene:  Prevent apoptosis Rb gene: The first tumor suppressor gene in patient  with retinoblastoma p53: Guardian of the genome Because the accumulation of gene mutation and Natural selection, so the patient is aged Chart of the major signaling pathways relevant to cancer in human cells, indicating the cellular locations of some of the proteins modified by mutation in cancers. Can we treat cancer? 1. Conventional approaches to combating cancer Surgery Chemotherapy/Radiation Can not rid of all cancer cells 2. Gene therapy Tumor cells lack functional tumor-suppressor genes p53-bearing viruses Engineered adenovirus Immune response 3. Inhibiting the formation of blood vessels Angiogenesis: Cancer cells —growth factors —endothelial cells —form new vessels * * Chapter 12 1. About the concept of cell differentiation The process that a cell changes to carry out a specialized function: Marked by: Morphology / Structure / Function The different cell types of a multicellular organism contain the same DNA. A cell can change the expression of its genes in response to external signals. Differences in mRNA expression patterns among different cell types. Different cell types synthesize different sets of proteins. Gene expression can be regulated at many of the steps in the pathway from DNA to RNA to protein. The four essential processes by which a multicellular organism is made: Cell proliferation, Cell specialization, Cell interaction, and Cell movement. Human:  1014 cells, >200 cell types 分子杂交技术检测基因及其表达3. Combinational control and  Gene differentiated express  pp.416: 12-1:  2n (n=3, A,B,C) House-keeping genes:  Expressed in all cell types, essential for all cells Luxury genes:  Tissue-specific genes, expressed in special cells Sequential expression of various genes in early Drosophila embryo Includes: Dedifferentiation---Redifferentiation 去分化再分化The ability of a cell develops into a complete organism  植物细胞具有全能性，在适宜条件下可培育成完整植株，已广泛应用Transplantation of frog red cell nucleus indicated the nucleus of animal is totipotency( 全能性) A new organism created by the process of nuclear transplantation Dolly: A lamb with no father c The sheep star: Dolly 克隆能给人类带来什么？克隆动物是未来的制药厂克隆的爱因斯坦会懂“相对论”吗Has two abilities: (1)Self-renewing (2)Differentiating (1) Embryonic stem cells (2) Adult stem cells (3) Umbilical cord blood stem cells (4) Fetal stem cells (1) Monopotential stem cell (2) Pluripotent stem cells (3) Embryonic stem cells Two ways for a stem cell to produce daughters with different fates For repairing tissue damage caused by disease or injury, including: Diseases that impair brain function, such as Alzheimer's disease and Parkinson's disease  Spinal cord injuries  Blood diseases, including leukemias  Burns Adult stem cells can differentiate into a large number of different cell types. Turning blood into brain: Science, 2000, 290: 1779-1782 Turning brain into blood: Science, 1999, 283: 534-535 NSC+EGF & FGF: Growing See also: Current opinion in cell  biology, 13: 662-665, 2001 Production of differentiated cells from mouse ES cells in culture. Stem cells migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration. 利用干细胞可塑性Regeneration of new tissues from our own cells will not be far behind  Science, December 6, 2002: 1901 Tumor Benign tumors: Do not spread Malignant tumors —Cancers: Metastasize Benign tumor Malignant tumor (1) Cell proliferate uncontrollably (2) Invade and metastasize (3) Less well differentiated than normal cells or benign tumor cells (4) Have highly aberrant chromosome complements—Aneuploidy Pancreas cancer