Cancer Flashcards
Normal cells exhibit ____ _____, and do not survive or divide in absence of ____ from the ________ ___.
Cancer cells are immune to this mechanism because they lose their ______. They also secrete _____ that degrade ___ and facilitate ____.
Normal cells exhibit CONTACT INHIBITION, and do not survive or divide in absence of SIGNAL from the EXTRACELLULAR MATRIX.
Cancer cells are immune to this mechanism because they lose their CADHERINS. They also secrete METALLOPROTEASES that degrade ECM and facilitate INVASION.
Tumor suppressor genes, when mutated, usually result in ___ of function. Their inheritance pattern is _____, but pedigrees can appear _____ due to _____ __ _________.
2 classes of tumor suppressor genes:
- ____ genes (___, ____, ____), whose products prevent or _____ DNA damage. Mutation in these genes alone are not _____ itself, but promote ____ _____.
- _______ genes (___ and ____), whose products ____ cell division or induce _____. Loss of these proteins functions allows for uncontrolled _____.
Oncogenes, when mutated, usually result in ___ of function. Their products promote cell ____ and ____.
Tumor suppressor genes, when mutated, usually result in LOSS of function. Their inheritance pattern is RECESSIVE, but pedigrees can appear DOMINANT due to LOSS OF HETEROZYGOSITY.
2 classes of tumor suppressor genes:
- CARETAKER genes (MLH, ERCC1, BRCA1/2), whose products prevent or REPAIR DNA damage. Mutation in these genes alone are not ONCOGENIC itself, but promote FURTHER MUTATIONS.
- GATEKEEPER genes (RB AND P53), whose products INHIBIT cell division or induce APOPTOSIS. Loss of these proteins functions allows for uncontrolled CELL PROLIFERATION.
Oncogenes, when mutated, usually result in GAIN of function. Their products promote cell GROWTH and DIVISION.
Mutations in ______ genes cause familial cancer syndromes such as ______, ____, and ______.
Mutations in CARETAKER genes cause familial cancer syndromes such as LYNCH SYNDROME, XP, and FAMILIAL BREAST/OVARIAN CANCER.
___ of function mutation in Rb causes retinoblastoma
- sporadic is characterized with ___ tumors in __ eye of ___ family member.
- familial is characterized by ____ affected family members, ____ tumors, ____ tumors in each eye, usually occur at ___ age
- pupil appears ____ because tumor has displaced the ____
LOSS of function mutation in Rb causes retinoblastoma
- sporadic is characterized with SINGLE tumors in ONE eye of ONE family member
- familial is characterized by MULTIPLE affected family members, BILATERAL tumors, MULTIPLE tumors in each eye, usually occur at EARLIER age
- pupil appears WHITE because tumor has displaced the RETINA
Loss of __ renders cancer cells immune to apoptosis.
- ____ stimulates transcription of ____ ____ and ____ ____ proteins such as ____.
- multiple signal transduction pathways converge on ___ because it integrates information about many aspects of the cell
- ___ is intrinsically unstable but is stabilized in response to ____
Loss of P53 renders cancer cells immune to apoptosis.
- -53 stimulates transcription of CDK INHIBITORS and PRO-APOPTOTIC proteins such as BAX.
- multiple signal transduction pathways converge on P53 because it integrates information about many aspects of the cell
- P53 is intrinsically unstable but is stabilized in response to DNA DAMAGE
The major inputs that lead to stabilization of p53:
_____, which leads to activation of ____
-once p53 is stabilized by ____, ____ cannot bind
Growth factors, which lead to synthesis of ____ protein
___ protein encodes a ____ inhibitor, but acts to sequester _____, which usually ____ p53 to lead to _____-mediated degradation.
The major inputs that lead to stabilization of p53:
DNA DAMAGE, which leads to activation of PROTEIN KINASES
-once p53 is stabilized by P-LATION, MDM2 cannot bind
Growth factors, which lead to synthesis of p14ARF protein
P14ARF protein encodes a CDK inhibitor, but acts to sequester MDM2, which usually P-LATES p53 to lead to UB/PROTEASOME-mediated degradation.
p53 Mutations and Cncer
- p53 protein has no defined ___ Structure unless it’s bound to ____
- mutations destabilize p53, especially it’s _____ domain, which blocks it’s _____ activity
p53 Mutations and Cncer
- p53 protein has no defined TERTIARY Structure unless it’s bound to DNA
- mutations destabilize p53, especially it’s DNA BINDING domain, which blocks it’s APOPTOTIC activity
Viral oncogenes are originally derived from ___ of ___, and their normal role is to promote ____ ____. Now, the gene is regulated in the context of the virus.
Viral oncogenes are originally derived from GENOME of HOST CELL, and their normal role is to promote CELL DIVISION. Now, the gene is regulated in the context of the virus.
Oncogenic mutations lead to ____ activity of the protein.
Cell cycle pathway can be altered in different ways in different tumors:
- can _____ function of GFR
- can ____ deactivation of ras
- can ____ a GAP
- can upregrulate TFs like ____
- can inactivate ___ or component of ____ pathway
Oncogenic mutations lead to ____ activity of the protein.
Cell cycle pathway can be altered in different ways in different tumors:
- can INCREASE function of GFR
- can PREVENT deactivation of ras
- can INACTIVATE a GAP
- can upregrulate TFs like C-MYC
- can inactivate RB or component of TGF-B pathway
mTOR is a ____-gene/. mTOR pathway promotes _____.
Components of mTOR pathway:
- ____, a membrane phospholipid
- _____ which converts 1–>3
- ____
- Presence of 3 activates ____, which is a protein kinase that p-lates and _____ TSC.
- TSC is ____ of mTOR. Mutations in TSC cause ______.
- mTOR is a protein kinase which p-late multiple targets to promote protein synthesis and cell growth
- ____ is a phosphatase that converts 3 back to 1
mTOR is a ONCO-gene/. mTOR pathway promotes CELL DIVISION.
Components of mTOR pathway:
- PIP2, a membrane phospholipid
- PI3K which converts 1–>3
- PIP3
- Presence of 3 activates AKT/PKB, which is a protein kinase that p-lates and INHIBITS TSC.
- TSC is INHIBITOR of mTOR. Mutations in TSC cause TUBEROSCLEROSIS.
- mTOR is a protein kinase which p-late multiple targets to promote protein synthesis and cell growth
- PTEN is a phosphatase that converts 3 back to 1
C-MYC is a _____ (also ____) that promotes expression of about 15% of human genes.
In some tumors, this gene is ____
In others, a ___ ___ results in increased transcription of c-myc
If copies remain in chromosome, they form a _____
They may also be found outside of chromosome as _________
______ lymphoma results from c-myc activation.
- classified by tumor of _ _____, cells that produce ____
- translocation puts c-myc under control of ____ gene enhancer
C-MYC is a TF (also ONCOGENE) that promotes expression of about 15% of human genes.
In some tumors, this gene is DUPLICATED
In others, a CHROMOSOMAL TRANSLOCATION results in increased transcription of c-myc
If copies remain in chromosome, they form a HOMOGENOUSLY-STAINING REGION
They may also be found outside of chromosome as DOUBLE-MINUTE CHROMOSOMES
BURKITT lymphoma results from c-myc activation.
- classified by tumor of B LYMPHOCYTES, cells that produce ABs
- translocation puts c-myc under control of ANTIBODY gene enhancer
CML cells contain a ____ which results in constitutive activity of protein kinase ____.
-reciprocal translocation between chromosomes _ and _ lead to Philadelphia chromosome expressing __/__ chimera.
CML cells contain a TRANSLOCATION which results in constitutive activity of protein kinase C-ABL.
-reciprocal translocation between chromosomes 9 and 22 lead to Philadelphia chromosome expressing BCL/ABL chimera.
Ras is an ____. It is part of ras-like family.
Ras:
Rab:
Ran:
Rac:
- Ras binds _____ (Active) and ____ (inactive).
- slow intrinsic ____ activity is stimulated by ____ such as ___ (Mutations in this protein lead to _____)
- replacement of ___ with ___ is stimulated by ____ Such as ____.
Proteins that contain a ras homology domain: ____ factors, large __ proteins, ____ which function in budding of membrane vesicles, and ____ and ____.
-____ mutations in ras mostly are ____ and _____ _______. They greatly reduce ____ activity, so it spends most of it’s time in ___ state.
Ras is an ONCOGENE. It is part of ras-like family.
Ras: RECEPTOR SIGNALING AND CELL DIVISION
Rab: TRAFFIC OF MEMBRANE VESICLES
Ran: NUCLEUS/CYTOPLASM TRAFFIC
Rac: ACTIN CYTOSKELETON
- Ras binds GTP (Active) and GDP (inactive).
- slow intrinsic GTPase activity is stimulated by GAP such as NF1 (Mutations in this protein lead to NEUROFIBROMATOSIS)
- replacement of GDP with GTP is stimulated by GEFs Such as SOS.
Proteins that contain a ras homology domain: TRANSLATION factors, large G proteins, DYNAMINS which function in budding of membrane vesicles, and MYOSIN and KINESIN.
-ONCOGENIC mutations in ras mostly are GLY-12 and GLN-61 AA SUBSTITUTIONS. They greatly reduce GTPase activity, so it spends most of it’s time in ACTIVE state.
Oncogene Addiction Hypothesis: some cancers are reliant on one ____ ___. If it is targeted, the medication can kill the tumor.
Oncogene Addiction Hypothesis: some cancers are reliant on one DOMINANT PATHWAY. If it is targeted, the medication can kill the tumor.
CML is characterized by ____ expansion as well as increased numbers of ____ cells and ____.
- often discovered by _____ (expansion of _____ series)
- symptoms are ____, ____, ___, ____ and early ___ due to ____.
-the cells are ____ normal but ____ abnormal (contain ___ levels of ____)
CML is characterized by MYELOID expansion as well as increased numbers of PRECURSOR cells and PLATELETS.
- often discovered by CBC (expansion of NEUTROPHIL series)
- symptoms are FATIGUE, WEIGHT LOSS, LOW GRADE FEVERS, SWEATING, EASY BRUISING and early SATIETY due to SPLENOMEGALY.
-the cells are MORPHOLOGICALLY normal but CYTOCHEMICALLY abnormal (contain LOW levels of LEUKOCYTE ALKALINE PHOSPHATASE)
