1. Cancer Biology Jasmina Makarevic
ATTA-UR-RAHMAN SCHOOL OF
APPLIED BIOSCIENCES (ASAB)
Cancer Biology Jasmina Makarevic
Fall Semester 2016

2. Stem cells Def: Cell type within a tissue that is capable
of selfrenewal and is also capable of generating
daughter cells that develope new phenotypes,
including those that are more differentiated than
the phanotype of stem cell.
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3. Cancer cells and stem cells
ES cells and cancer cells can form teratomas (benigne tumors formed by
embryonic stem cells in which a wide variety of differentiated cell types
are found). They are difusse mess of cells.
Many of the stem cell surface receptors are also expressed on cancer cells.
Similar genes are expressed in both cell types. Also a ras-like gene Eras is
expressed in mouse ES cells, which may give these cells tumor-like
properties.
Cancer Cells acquire the machanery for cell proliferation that is expressed
in tissue stem cells. But what they lose: Feedback systems to know when
to stop proliferation and to start differentiating!
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4. Transformation of stem cells?
Are stem cells the targets for carcinogenic transformation?
Reya et al.:
Stem cells already have the machinery for self-renewal turned on and it
would require fewer genetic or epigenetic manipulations for a cell to be-
come a cancer cell than if they had to turn all these genes in the novo.
Stem cells by their vary of nature are set up to proliferation for several
population doublings and thus have a greater oppurtunity for carcino-
genic mutations to accumlate than in most mature cell types.
Cancer cells lose the ability of differantiation after progression!
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5. Growth Factors
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6. How does GF work?
As protein kinasen- an enzyme that removes a high-energy phosphat group from ATP and transfer s it to a suitable protein substrat.
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7. Actions of protein kinases
One protein kinase can
phosphorylate multiple
distinct substrat proteins
within a cell.
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8. Structure of the EGF receptors
Cytoplasmic domain once activated emits signals that induce a cell to grow or divide:
Cytoplasmic domain activated proceeds to phosphorylate tyrosines on certain
Cytoplasmic proteins and causes proliferation.
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9. Structure of tyrosine kinase receptors
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10. Different Growth Factors
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11. The EGF receptor and v-ErbB
An altered growth factor receptor can function as an oncoprotein!
Oncoproteins like ErbB2, HER2 or Neu are a kind of truncated EGF receptors
which don not need ligands to be activated!
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12. Deregulation of receptor firing
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13. Tyrosin kinase GF receptors
Summary statistics (2012)
Tyrosin kinase GF receptors
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14. Autocrine growth factors in human tumors
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15. Notch-Receptor Active form of Notch function as an
Transcription Factor!
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16. The Patched- Smoothened Signaling System
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17. The ras signaling cycle
GEF: Guanin
nucleotid factor
GAP: GTP-ase
activating proteins
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18. Alternative mechanisms of transformation by Ras
Ras also can also aktivate
EGF receptora upstream!!!
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19. Summary statistics (2012)
Conclusion
Without Growth factors, they would not be an activation of the cell signaling
pathways and no proliferation!
In the next lecture we will have a closer look:
Important cell signaling pathways
Cell Cycle check points/Tumor supressor genes
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20. Thank You for Your Attention!
Jasmina Makarevic