Cell Signalling and Oncogenes Flashcards
What do all signalling pathways involve?
A chemical messenger, a receptor, and a cellular response.
Name some rapidly dividing cells
epithelia, blood cells
Name some slowly dividing cells
nerve cells
What can signal transduction result in?
Alterations in:
Cell metabolism
Gene transcription
Cell shape
What are proto-oncogenes?
Genes that code proteins that help regulate cell growth and differentiation
What is an oncogene?
A proto-oncogene that has become activated due to mutation or increased expression
What are the two factors in increasing genetic instability?
Oncogene activation
Tumour suppressor gene inactivation
What are the main initiating agents for cancer?
Environment
Genetic susceptibility
What do oncogene activation and tumour suppressor gene inactivation lead to?
Replicative senescence
Programmed cell death
Differentiation
Cell cycle checkpoint control
What are the main mutations in cancer?
Deletion, insertion, substitution, amplification and translocation
What can be deleted?
Base pair(s)
Gene
Chromosome
What can be inserted?
Base pair(s) Novel insertion of viral DNA
What can be substituted?
Base pair(s)
What can be amplified?
Gene
Region
Chromosome
What can be translocated?
Chromosome
What proteins are encoded by oncogenes that act on cell surface receptors?
Growth factors e.g. PDGF
What proteins are encoded by oncogenes that act on intracellular proteins due to extracellular signalling?
Growth factor receptors e.g. EGF receptor (erbB)
What proteins are encoded by oncogenes that are activated by transmembrane receptors?
Protein kinases or proteins that activate protein kinases e.g. Ras (ras), Raf (raf), Src (src)
What proteins are encoded by oncogenes that act within the cell?
Proteins that control the cell cycle e.g Cyclin D (bcl-1)
What proteins are encoded by oncogenes that regulate cell survival?
Proteins that affect apoptosis e.g. Bcl-2 (bcl-2)
What proteins are encoded by oncogenes that act on DNA?
Transcription factors e.g. Myc (myc)
Give 2 examples of insertional mutagenesis caused viruses?
Human papillomavirus 16/18 and cervical cancer
Hepatitis B virus and hepatocellular cancer
How common is insertional mutagenesis?
Relatively uncommon in human cancer, but has 2 high profile examples.
What chromosomal translocation occurs in chronic myeloid leukaemia?
9;22 (c-abl (9) truncated onto bcr (22))
What effect does the 9;22 CML translocation have?
Fusion protein has abnormal tyrosine kinase activity
What chromosomal translocation occurs in Burkitt’s lymphoma?
8;14 (c-myc (8) truncated onto igh (14))
What effect does the 8;14 Burkitt’s lymphoma have?
Stronger promotion of c-myc gene leading to constitutive MYC expression in B cells (gene at 14q32 = IgH locus enhancer)