Neoplasia 3- evasion of apoptosis Flashcards
_______ is the prototypic anti-apoptosis gene
BCL2
how can the BCL2 gene be activated?
Can be activated by translocation from chromosome 18 to the Ig heavy chain locus on chromosome 14
(shift from chromosome 18 to 14)
what is the result of BCL2 over-expression? where is this situation usually seen?
Results in steady accumulation of cells (prevents apoptosis)
– often seen in “low-grade” lymphomas
p53 will upregulate ____, which triggers apoptosis
upregulates BAX gene
its a balancing game between BLC2 and BAX
Tumors cannot grow larger than 1 or 2 mm in diameter unless what occurs?
they are vascularized
how does Angiogenesis facilitates metastases ?
it provides the neoplastic cells access to the vasculature
what are the 2 major steps in invasion/metastasis?
1) invasion of the extracellular matrix
2) vascular dissemination and adhesion/homing of tumor cells
how do tumor cells invade the extracellular matrix?
- Detachment of tumor cells from one another
- Attachment of tumor cells to matrix components
- Degradation of extracellular matrix
- Migration of tumor cells
how can the distribution of tumor metastasis be predicted?
can generally be predicted by the location of the primary tumor and its vascular or lymphatic drainage
lung cancer spreading to adrenal glands, but almost never to skeletal muscle, is an example of what?
organ tropism
what 2 ways can organ tropism occur?
A) Adhesion molecules:
-Organ-specific endothelial adhesion molecules bind tumor cell ligands
B) receptor mediated homing:
-Chemokine receptors on tumor cells home to sites where specific ligands are readily produced
what is Hereditary nonpolyposis colon cancer syndrome? what causes it?
- familial cancers of the colon
- resulting from defective genes involved in DNA mismatch repair
- and evidence of microsatellite instability (MSI).
microsatellite instability (MSI) is seen in ____% of colon cancers
15%
what is Xeroderma pigmentosum? what causes it?
- defective nucleotide excision repair system
- Sunlight (UV light) causes pyrimidine cross-linking in DNA, halting replication
**inability to repair UV damage
what (4) disorders are associated with characterized by hypersensitivity to DNA damage (AKA “fragile DNA” diseases)
Bloom syndrome
ataxia telangiectasia
Fanconi anemia
familial breast cancers (BRCA1 & 2)
what is meant by the concept of “Multistep Carcinogenesis ”?
Cancers typically exhibit multiple genetic alterations including activation of several oncogenes and two or more cancer suppressor genes
what characteristic change as tumors progress through successive “generations”? (how do daughter cells differ)
- they change due to the acquisition of multiple mutations during tumor growth
- results in numerous “subclones” with different characteristics
CML (“Philadelphia chromosome”) is an example of what Karyotypic change?
Balanced Translocations
- translocation between chromosome 22 and 9. As a result, 22 appears shortened
what types of cancers result from karyotypic deletions?
– retinoblastoma (Rb)
- colon cancer
- oral cancer
neuroblastoma and breast cancers are both the result of what Karyotypic change?
Gene amplification
chronic myelogenous leukemia is the result of balanced _________
translocation
- ALB onconogene is translocated from chromosome 9, onto the BCR locus of chromosome 22
During CML, the BCR-ALB hybrid gene will code for what to be produced?
Tyrosine kinase
what are the 3 major classes of carcinogens?
1) chemical
2) radiant energy
3) onconogenic viruses
Percival Pott was the first to discover __________
chemical carcinogens
- linked scrotal cancer (ouch) to the soot from chimneys
