MCM 2-13 Growth Control Flashcards Preview

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Flashcards in MCM 2-13 Growth Control Deck (41)
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internal factors that regulate growth control

apoptosis, terminal differentiation, senescence



programmed cell death

occurs during normal development (formation of digits, etc.)

most cells require trophic factors to stay alive, in absense of these signals, cells initiate apoptotic pathway

-signaling cascade = activation of cystein proteases called caspaces from procaspase forms
-these digest important intracellular structural proteins like lamin and cytoskeletal proteins.


what happens to cells when they apoptose?

apoptotic cells shrink and fragment, releasing small, membrane bound apoptotic bodies that are phagocytized by macrophages.
-This controlled waste disposal prevents cytosolic contents from leaking into the EC space which would cause inflammation (this happens in necrotic cells)


terminal differentiation

process by which the specific gene upregulatory proteins of certain differentiated cells (neuron, cardiac muscle cells) prevent the cells from dividing further. Significant barrier to recovery from spinal and cardiac injuries.



process by which cells of a given cell line stop dividing

due to absence of telomerase (an enzyme with an RNA portion used to add six-base repeats to telomeres)

-allows for complete syntehsis of the lagging strand in DNA replication

when telomeres get too short, p53 activated, leading to senescence. This limits unwanted proliferation and prevents replication of incomplete and unstable chromosomes.

Most adult tissues lake telomerase


external factors that regulate growth control

Growth factors, Cell ahdesion (Cell-EM interactions and Cell-cell interactions)


Growth factors

chemical messengers that influence cell growth. They are concentration and cell-type specific.

They can act locally (PDGF released by platelets to stimulate wound repair)

or systemically (erythropoetin produced by kidney to stimulate red blood cell differentiation in bone marrow)


Cell Adhesion

Cell-ECM interactions - anchorage dependant cell growth. ADhesion to the ECM stimulates cells to proliferate. Interactions via folal adhesions stimulate convergent pathways.

Cell-Cell Interactions - contact inhibition. Serve as negative regulator of cell proliferation (wound repair)


how do normal cellular genes become oncogenic?

normal cellular genes with potential to become oncogenic are called proto-oncogenes.

protooncogense have important normal cellular functions: stimulate cell growth and/or proliferation.

conversion to oncogene results in elevation/unregulated activity

a mutuation in even a single allele of proto-oncogene can cause abnormal growth/differentiation.


proto-oncogene mutations are ________ and of what types?

proto-oncogene mutations are somatic and of the following types

deletions or point mutations in the coding sequence - leads to production of hyperactive protein in normal amounts

gene amplification - leads to normal protein being overproduced

chromosome rearrangement - when gene is moved into the vicinity of a strong enhancer, normal protein is overproduced
when the gene is fused to an actively transcribed gene, a fusion protein is either produced in large amounts, or is simply hyperactive


how tumor suppressor genes regulate growth

TSG's generally function to inhibit growth by opposing activity of proto-oncogenes.

both alleles of TSG must be lost before uncontrolled growth will occur (loss of heterozygosity)

cancer-predisposing genotypes related to tumor suppressor genes are inherited. - one can inherit a single bad tumor suppressor allele and be more likely to develop cancer due to a somatic loss of the other tumor suppressors alleles function.


why do most cancers involve cumulative mutations?

cells undergoing uncontrolled growth will form tumors.
once they obtain the ability to invade other tissues and metastasize, they form malignant tumors and have become cancer cells.

the transition between these two states typically occurs in steps, each marked by a new mutatiion in a different proto-oncogene or TSG.

because of this mutation profile that develops, oncotherapies are best tailored to the individual


3 types of factors that regulate growth control

1. cell lineage (internal)
2. external/diffusable factors (growth hormones)
3. cell/cell and cell/ECM adhesion interactions


describe cell lineage control of cell growth

internal control of G1/S transition

apoptosis - carefully controlled waste disposal

also occurs in normal development (digitization and neuronal connection trimming)

-occurs in normal adult cells (lining of gut, mammary tissue post lactation)

-also occurs as a result of checkpoint error during DNA replication cycle


improper apoptosis during digitization



what causes neuronal cell apoptosis

during development, absense of trophic factors (survival factors) excreted by target cells

cell death balances the number of neurons to number of target cells


describe apoptotic cells

cells shrink, form membrane blebs that fragment, releasing small membrane bound apoptotic bodies that are phagocytized by macrophages

-prevents inflammation

as opposed to necrotic cells that swell, burst, and cause huge inflammation


describe a neuron that is receiving enough trophic factors vs one that is not

receving enough trophic factors - initiates signaling cascade that causes pro-apoptotic factor BAD to get sequestered in cytosol. cell survives.

not receiving enough - BAD remains active, interacts with anti-apoptotic proteins in mitochondria.
End result = inhibitory role on BAD is lost, ions enter mitochondria. cytochrome c released. this gives rise to a catalytic cascade, which causes the internal degredation and apoptotic bodies start to form and get released.


Terminal Differentiation

Second internal mechaism of G1/S transition control

some cells stop dividing (express a novel set of genes for the specialized function of cell)

ex) neurons and cardiac muscle cells

causes barrier to spine injury and heart disease treatments



Third mechanism of internal control of G1/S transition

cells in culture will stop dividing after 50-100 divisions due to absence of enzyme called telomerase

this causes the telomeres to shorter with each round of replication, signaling pathways (including p53 upregulated which upregulates p21 CDK inhibitor, blocks cells in G1

important for limiting unwanted differentiation



an enzyme, more specifically a ribozyme (half protein, half RNA)
-adds 6 base pair noncoding repeats to ends of chromosomes (parental)

allows for more complete syntehsis


most ______ cells lack telomerase

somatic cells


growth factors

a type of external factor influencing cell cycle movement

-some act locally (PDGF) some act distantly (erythropoietin)


Cell-ECM interactions

a type of external factor influencing differentiation/cell cycle/growth

"anchorage dependent cell growth" e.g. control of cell proliferation/differentation at the skin epidermis

healthy cells that are suspended will not proliferate, must be given patch to adhere to.

cells allowed to adhere to small amounts of ECM protein (fibronectin, collagen) will form a few focal adhesions and some will proliferate

Cell adhesion to ECM can induce proliferation


cell-cell interactions

cell density dependant growth inhibition = contact inhibition (important in wound repair)


cell adhesion to ECM, not just structural but can also control

cell fate


describe skin epidermis example

skin epidermis is hostile, constantly sloughing off

only cells in contact with basal lamina can undergo cell division - they are experiencing anchorage-dependent cell growth/differentiation

when these cells escape, integrins get downregulated, and will start differentiating into skin cells and upregulate adherins and IF to form cell:cell desmosomes that are important for the barrier function of skin

process goes awry - tumors


growth control is a balance between

stimulatory and inhibitory signals (kinase vs phosphatases) (GEFs vs GAPS)

example is MAP kinase pathway - cascade of various kinase signaling molecules activate downstream kinases that activate downstream molecules

when kinases activate they are a phosphorylated intermediate

phosphatases can dephosphorylate, causing deactivation

RAS is activtated by GEF, inhibited by GAS. balance of GEF and GAS determines if pathway is activated


characteristics that cancer cells may or may not exhibit

do not senesce (active telomerase or inactive p53)

lack growth factor dependence

lack anchorage dependence (will grow in suspension )

no-cell:cell contact inhibition (cells will pile up on top of each other and form Foci)


most cancers result from

mutations affecting the function of proteins involved in important regulatory signal transduction pathways

2 main classes - oncogenes and tumor supressor genes

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