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Nutrition 3701

CANCER- 6 October 2010


Outline for the day



Tumour suppressor genes (antioncogenes)

Oncogenes, growth factors, hormones and their receptors


    -current dogma is that cancer is the accumulation of a series of genetic insults (alterations to the gene sequence)

    -review of gene sequence

    -base sequence adenine, thymidine, guanidine, cytidine

                    -importance of base sequence-

                                    this is important in-transcription -copying of DNA to make RNA

                                    -translation-interpreting the RNA sequence to make proteins

    -genes that are altered in terms of their sequence are those that are involved in the normal cellular processes such as cell cycle regulation, differentiation and signalling

    -cell cycle-cellular reproduction

    -differentiation- when cells change into different types of cells

                            -cells start out as stem cells

                            -as cells differentiate they send out various chemical messengers (signalling messengers) that promote further differentiation of cells

    -as cells are under the control of DNA, certain alterations in that DNA can alter the cell cycle, differentiation and chemical messenging resulting in cells that are out of control- these out of control cells continue to reproduce uncontrollably and disrupt the structure and integrity of other cells resulting in loss of function of cells

-alterations to gene sequence-due to insults such as radiation, viruses, chemicals and diet

-there are DNA repair mechanisms but if these mechanisms fail to work then one is left with a permanently altered DNA- it is possible to pass these permanently altered genes to ones offspring

-consequently it is possible to carry out pass damaged or pro-cancerous genes from one generation to the next

-for example the BRCA-1 gene has been identified and linked to breast cancer in current and succeeding generations of women who have the BRCA-1 gene

-once a gene has been modified to a pro-cancerous form and transmitted to future generations there are some cases where it is difficult to undo or overcome the damaging effects of the pro-cancer gene

Protooncogenes and Antioncogenes

        Proto-oncogenes-genes that can be converted to oncogenes –oncogenes favour the loss of cellular control

                    -liken this to an accelerator on a car

        Anti-oncogenes-genes that favours the maintenance or regaining of control

                    -liken this to a brake on a car

        -consequently- maintenance of cellular control depends on a constant balance between protooncogenes and the antioncogenes

        -indeed in a normal well-controlled cell both protooncogenes and the antioncogenes are active

        -protooncogenes-favour cell reproduction

        -antioncogenes-prevention of cell reproduction

        -if protooncogenes and the antioncogenes activities are not in the correct balance then cancer develops

        -examples of protooncogenes and the antioncogenes

        -protooncogenes-growth factors and growth factor receptors

                                    -protein kinases

                                    -mediators of cell transduction

                                    -DNA binding proteins


                                    -induce cellular apoptosis

                                    -gating genes- will not allow a cell to pass beyond a certain point unless all the correct signals are in place-viewed as early

                                                                                                 warning system

Messages normally go out are those meant to keep the body cancer free

                    THE RED CAT ATE THE OLD RAT

Conversion of proto-oncogenes to oncogenes via

                    -point mutations/transversions

                            -single base change in codon

                            -frequently result from carcinogens and radiation

                            -single base change results in sense or nonsense mutations of message

                                            -sense- message is still understandable

                                                        THE RED CAR ATE THE OLD RAT

                                            -nonsense-message is unintelligible

                                                       THE RED CAX ATE THE OLD RAT

                                                Nonsense message results in stop codon and truncated protein whose signal in


                    -frameshift mutation

                                        result from insertions or deletions of a single nucleotide or of large amounts of DNA
                                                -frequently results in unreadable sequence

                                                                                THE REC ATA TET HEO LDR ATZ


                                -instead of 2 copies of a gene have at least 10 to hundreds of copies of a protooncogene-push to cell replication cannot be

                                                                         overcome by compensatory cellular mechanisms


                                        -fusion of 2 genes resulting in a novel protein

                                                    gene A-THE RED CAT ATE THE OLD RAT

                                                    gene B-THE DOG SAW THE NEW FLY

                                        after fusion

                                                     gene A-THE RED CAT SAW THE NEW FLY

                                                     gene B-THE DOG ATE THE OLD RAT

                                                -results in message that may promote cancer

Tumour suppressor genes

                                -alterations in these reduce braking mechanism and control is lost

Oncogenes, growth factors, growth hormones and their receptors

                            -all of these are abnormally expressed in malignant cells

                          -overexpression of oncogenes, growth factors, growth hormones and their receptors in malignant (out of control cancerous) cells

                                                                         resulting in unfettered cell growth