LECTURE 10 PART 2 Flashcards
in Burkitt Lymphoma, the expression of ____ is enhanced
how?
c-myc
by its association with the promoter regions of immunoglobulin genes
in which type of cancer is the Philadelphia chromosome in 95% of patients?
CML (chronic myelogenous leukemia)
a shortened 22 chromosome and longer 9 chromosome
they undergo fluroescence in situ hybridization
what is TGF-B
a tumor suppressor gene
regulates apoptosis
when doesn’t function, apoptosis doesn’t happen and the cancer cell evades it
Forms SMAD2/3-SMAD4 complex which:
activates the transcription of cell cycle suppresors (INC)
represses transcription of c-Myc (proliferator)
explain the signaling function of PTEN
normally, when growth factor binds to receptor, PIP2 is phosphorylated which produces PIP3
PIP3 is regulated by PTEN
explain what happens when the level of PTEN is decreased
normally, the amount of PIP3 is regulated by PTEN
when the level of PTEN is decreased PIP3 accumulates bc it is not dephosphorylated well by PTEN, and Akt is increased
this decreases apoptosis and leads to cell cycle progression. increased ROS, and increased mTOR to promote cell survival
UNCONTROLLED CELL PROLIFERATION AND CANCER
_____ is a principle mediatory of growth arrest, senescence, and apoptosis
p53
p53 has a checkpoint where?
at G1 - checks the DNA integrity and triggers cell death if needed
explain how p53 induces apoptosis
triggered by stress/DNA damage, p53 is activated
p53 binds Bcl-2 and bcl-XL and activates cytosolic Bax which induces apoptosis
what is Retinoblastoma?
child inherits it
germline mutation in 1 allele of the Rb gene AND a second somatic mutation in the retina – leads to development of RETINOBLASTOMA
in RARE cases, child is born with 2 normal Rb alleles and for tumor development, there must be 2 INDEPENDENT SOMATIC mutations
ALSO LOH (loss of heterozygosity) can result in retinoblastoma – there is 1 germline mutation and 1 normal allele and the normal allele disappears
what is “two hit origin”
term for retinoblastoma
one mutation isn’t sufficient for tumor progression - must be 2
what is epigenetics
diverse mechanisms that control gene expression, INDEPENDENT of the actual DNA sequences that encode proteins
epigenetic mechanisms orchestrate physiologic processes. function normally to prevent tumors
HOWEVER, when dysfunctional, may drive tumor development
what are some triggers for epigenetic alterations and what are some direct consequences?
NONCODING DNA sequences may be altered - like the promoter or enhancer
or the DNA sequence may remain intact and environmental factors like hypxia, aging, etc can cause epigenetic alterations
resulting in increased tumorigenesis activities and decreased tumor suppressor activities
90% of cancers are linked to….
somatic mutations and environmental factors
many environmental causes of cancer and risk factors are associated with…….
CHRONIC INFLAMMATION
Name some local effects of cancer
obstruction and pressure - esp if tumor is near organs
ulceration and bleeding - mainly in colonic, gastric, and renal carcinoma
infection due to luminal obstruction - such as pneumonia, UTI
rupture - in ovary/bladder/colon
name some systemic effects of cancer
fatigue
anemia
cancer cachexia (progressive weakness, loss of appetite, weight loss)
paraneoplastic syndrome
why is fatigue a systemic effect of cancer?
due to biochemical changes and loss of muscle function
why is anemia a systemic feature of cancer
malnutrition
chronic bleeding
cytotoxic drugs
bone marrow involvement
what is cancer cachexia
progressive weakness, loss of appetite, anemia, weight loss from tumor mass and spread, increased metabolism, and production of cytokines
A SYSTEMIC EFFECT OF CANCER
what is paraneoplastic syndrome
a systemic effect of cancer
clinical states that occur from products released from the tumor itself
in lung carcinoma - cushing’s syndrome bc of lot of ACTH
inappropriate ADH secretion
Colorectal - hypocalcemia
fibrosarcoma - hypoglycemia bc of insulin activities
