Oncogene and Proto-oncogene

in this slide diffrent types of gene responsible for cancer
what is protooncogene

1. Proto-oncogene The genes that involve in the cancer can be divided into following types. Proto-oncogenes Proteins encoded by proto-oncogenes may function as growth factors or their receptors, signal transducers, transcription factors, or cell cycle components. Proto Oncogenes products regulate the cell growth, division of cells, prevent cell differentiation and regulate apoptosis.

2. Examples of Proto oncogenes is the Her2 gene. This gene codes for a transmembrane tyrosine kinase receptor called Human epidermal growth factor receptor. This protein receptor is involved in the growth repair and division of cell in the breast. Wnt , Myc , Fos /Jun, RTK, Ras MAP kinase are Proto oncogenes. Products of proto oncogenes genes are essential for cell survival and growth. Mutations in proto-oncogenes convert proto-oncogenes into constitutively active cellular oncogenes that are involved in tumor development.

3. Protooncogenes convert it into oncogenes by the following type of mutation Point mutation: a protooncogene is convert into oncogene by insertions or deletions that give rise overactive gene product. This mutation also leads to an increase in transcription rate. For example, a change in ' ras ' oncogene includes H- ras , K- ras , and N- ras . The proto-oncogene code for signal transduction. A GTP-binding protein has GTPase activity that become active to inactive by hydrolysis of GTP to GDP. The RAS genes, of which there are three in the human genome (HRAS, KRAS, NRAS), were discovered initially in transforming retroviruses. The single most common abnormality of proto-oncogenes in human tumours is Point mutation of RAS family genes.

4. When RAS is bounded with GDP it is inactive when RAS is bounded with GTP it is active. The activated RAS stimulates downstream regulators of proliferation, such as the mitogen-activated protein (MAP) kinase cascade GTP hydrolysis, which converts the GTP-bound, active RAS to the GDP-bound, inactive form. Guanine nucleotide exchange factors turn on signalling by catalysing GAPs terminate signalling by inducing GTP hydrolysis. GDP GDP GTP GTP GDP GTP GEF GAP G α G β G γ G α G β G γ G α G β G γ G α G β G γ

5. Several different point mutations of RAS have been identified in cancer cells. The point mutation reduce the GTPase activity of the RAS protein, thus cell is forced into a continuously proliferating state. In Colon, lung and pancreatic tumors point mutation is found in KRAS. In Bladder and Kidney tumors point mutation is found in HRAS. In Melanomas tumors point mutation is found in NRAS and in BRAF. In Hepatoblastoma, hepatocellular carcinoma tumors point mutation causes overexpression of b-catenin. b-catenin is involved in WNT signal transduction. In Acute lymphoblastic leukemia ABL is translocated. ABL is a Nonreceptor tyrosine kinase.

6. Protein Biosynthesis MicroRNAs Cell adhesion DNA repair Translation Metabolism Cell Cycle Signal Transduction Transcription

7. Myc (c- Myc ) is a regulator gene that codes for a transcription factor. Play important role in cell cycle, apoptosis and cellular transformation. In Burkitt lymphoma, a B-cell tumor the Myc gene is translocate to Burkitt lymphoma, a reciprocal translocation between chromosomes 14 and 18 is also extremely common in follicular B cell lymphoma. Fusion of the BCL-2 gene with the IGH locus, resulting in anti-apoptotic protein BCL-2 overexpression. MYC is amplified in some cases of breast, colon, lung, and many other carcinomas. The related N-MYC and L-MYC genes are amplified in neuroblastomas and small-cell cancers of the lung, Dysregulation of MYC expression resulting from translocation of the gene occurs in Burkitt lymphoma, a B-cell tumor . Diffuse large B-cell lymphoma Burkitt lymphoma Mantle cell lymphoma Follicular lymphoma C-3,14 C-8,14 C-11,14 C-18,14