Class Notes (839,471)
Canada (511,354)
Biology (2,437)
BIOLOGY 2B03 (285)


11 Pages

Course Code
Richard B Day

This preview shows pages 1,2 and half of page 3. Sign up to view the full 11 pages of the document.
April 2 , 2013 Biology 2B03: Cell Biology Tumorigenesis Cancer Biology - tumorigenesis can stem form errors in signalling pathways and cell cycle regulation mechanisms that we have discussed Objectives - identify the characteristics of cancel cells - describe the hallmarks/acquired capabilities of cancer cells - describe the multi-hit model of tumor development - identify the categories of genetic targets - differentiate between tumor suppressors and oncogenes Stages of Tumor Development - benign tumor:  slow growth, localized  closely resemble normal cells  express normal cell-specific markers  can become malignant as they have gained more of the activities typical of cancerous cells - malignant tumor:  divide rapidly  high nucleus/cytoplasm ratio  less differentiated than normal cells  loss of cell-specific markers  invade surrounding tissue - pap smear to detect cervical cancer Human Liver Tumor - high nucleus/cytoplasm ratio in dark staining tumor cells - tumor cells:  less differentiated  characteristics of rapidly growing cells including high nucleus to cytoplasm ratio  prominent nucleoli  few specialized structures (undifferentiated) Metastasis - spread of tumor cells, enter circulatory system - proliferate and establishment of 2 area of tumour growth - loss of cell-specific markers - once they enter into the circulatory system they can go any where in the body, some of these cells can rest and stop in a second area - secondary tumor is usually fatal - same initial tumor that has moved - metasized melanosarcoma invading the liver - can see melanin in cells that are now in the liver - accumulating many mutations and not undergoing regulated cell death The Hallmarks of Cancer - which genes are disrupted, resulting in each of these acquired characteristics? - But one or two processes alone may be affected April 4 , 2013 Genetic Basis for Cancer - Change in the genetic level attributed to cancer - Mutations that occur during adult lives - Result of cells native to our body: our own cells changing in some way - Normally grow in a monolayer: all cells are toughing, the contact is inhibitory and prevents further division - Transformation by adding a piece of the genome that came from human cancerous cells – narrowing down to the pieces capable of giving these changes in behaviour - Foci of cells divide more rapidly, pilling on top of each other - Genetic markers are gone - Added extra DNA but we haven’t added new cells - Cells are aneuploidy, not undergoing cell death, can divide indefinitely, can undergo cell division without having growth factors st - 1 evidence that genetic material can cause tumorigenesis: DNA from cancer cells transform cultured cells: oncogenic transformation – taking a normal cell and transforming it into a cancer cell - transformed cells :similar to tumor cells - altered morphology, reduced need for growth factors, altered chromosome complement (aneuploidy), avoid apoptosis - transformed cells are rounded and less adherent - do not enter G 0 Oncogenes - any gene that encodes a protein capable of transforming cells in culture or inducing tumors in animal - normal cellular gene called a proto-oncogene - can also induce tumours in animal models - e.g.:  proto-oncogene = ras the normal cellular gene  oncogene = ras , codes for constitutively active Ras protein - but, is one oncogene enough: we need more than one gene to contribute to the formation of tumours Two Broad Classes - proto-oncogenes: mutants (oncogenes) = increased activity - tumor suppresors: mutants = loss of restraint, components involved in checkpoints - loss of cell regulation that gives rise to cancer is due to genetic damage in somatic cells, but increases susceptibility linked to inherited mutations. - More susceptible to cancer if you have inherited genetic damage related to cancer Multi-Hit Model - evidence indicates that tumorigenesis is a multistep process that reflect genetic changes - evidence: 1) analysis of tumours - a tumour is derived from a single cell (clonal colony of a single cell) - analysis of DNA from cells within a human tumour shows that tumour cells share the same genetic mutations (somatic mutations) - mutations in multiple genes are needed to convert a normal cell to a malignant cell - note: somatic mutations: mutations in the DNA body cell (cells that are not part of the germline) share common somatic mutations. Share characteristics such as X-inactivation Human Colorectal Cancer - categorized based on the morphology of the tumour - first step – loss of function of APC (tumour suppressor) benign polyps. See increased cell proliferation. - Second step – cells then get some or all of the other mutations in varying order, Ras , DCC, p53. See uncontrolled cell proliferation - Third step, fourth step – mutations in tumour suppressors and/or oncogenes. Leads to malignant carcinoma and metastasis. - Cells skipping checkpoints making it more likely for other mutatiosn to accumulate - Process is slow at first then speeds up Multi-Hit Model - Line trends up toward the right hand side, consistent with multi-hit model - Different rates at which these cancers occur, some cells have a tendency to accumulate mutations over time - evidence 2) epidemiological studies - cancer incidence increases exponentially with age, mutations, accumulate in multiple genes over time - single mutation gives aberrant cell growth advantage over normal cells, 2 nd mutation add another tumor ability (angiogenesis for eg), 3 mutation allows cell and its progeny to escape into blood, seen in cooperativity of oncogenes - evidence: 3) mouse model - adding DNA to induce tumours - cooperativity of oncogenes: progression is more rapid when mutations are both expressed - Myc or Ras activation alone: tumours occur in mice at low rate - High rate of tumourigenesis seen with more than one oncogene - Long latency of tumour formation also reflects need to acquire multiple mutations (not just in ras and myc) - As mice get older they have a higher rate of tumour indicating that mutations appear as we age Parallel Pathways of Tumorigenesis - aware of specific defects in individual patients in order to properly treat the patient The Genetic Basis of Cancer - proto-oncogenes and tumour suppressors (checkpoint controls, DNA repair) - general: cancer cells acquire autonomy from external regulatory signals: lower requirement for growth-stimulatory signals and diminished sensitivity to inhibitor signals. Gain-of-Function Mutations in Proto-Oncogenes - most proto-oncogenes are essential and conserved - required for activating cell division - activation of proto-oncogene to oncogene involves gain-of-function mutation - classes of proto-oncogenes:  growth factors  hormone receptors (pathways that induce cell division)  signalling proteins e.g. Ras  transcription factors e.g. Fos, Myc  anti-apoptosis proteins (keep cells alive) Loss-of-Function Mutations in Tumour Suppressors - tumour suppressors usually inhibit cell proliferation (brakes of the cell), so loss of function = cancer - both alleles must be inactivated or lost to promote tumour development - classes of tumour suppressors:  hormone receptors (pathway that inhibit cell division)  pro-apoptosis proteins (remove damaged cells)  cell cy
More Less
Unlock Document

Only pages 1,2 and half of page 3 are available for preview. Some parts have been intentionally blurred.

Unlock Document
You're Reading a Preview

Unlock to view full version

Unlock Document

Log In


Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.