lecture 5 germline 2 Flashcards
difference between teratoma and teratocarcinoma
TERATOMA
mature
differentiated cells
benign
TERATOCARCINOMA immature undifferentiated EC cells -pluripotent -highly proliferative -able to metastasize
what are EC cells
embryonic carcinoma cells- malignant stem cells
what makes EC special
- stem cells that were able to be serially transplanted into other mice
- grown in culture, no signs of contact inhibition and could be established as permanent cell lines
Grows fast and kills host
what was brinsters 1974 experiment
injected EC cells into blastocysts. EC cells led to many different cell types
Demonstrates pluripotency of EC cells
what does EC form that shows evidence of pluripotency
embryoid bodies- EB
look like blastocyst: outer layer of cells but inner layer no organized
EC cells help do what
provide foundation for establishing mouse embryonic stem cell cultures as well as establishing human embryonic stem cells.
what two concepts from EC were used to made ES
- feeder cells
2. identification of growth factors
what is the major difference between EC and ES
EC are malignant
what are the three reasons teratomas or teratocarcinomas occur outside of the gonads
- PGCs never made it to the genital ridge, survived and mutated
- metastases of EC cells
- “existing” stem cell populations mutated
teratomas come from mutation of ___. what experiment showed this
germ cells
genital ridges grafted to adult mice= teratoma
grafts with steel (SI/SI)= no teratoma because Si/SI= no germ cells
TGCT
testicular germ cell tumors
results from mutations of PGC development
TGCT make up ___ % of testicular cancer
96
what goes wrong in PGC development that leads to TGCT
- abnormal cell cycle
- abnormal interactions with somatic cells
- reversion to pluripotency of adult germ cells
in TGCT, what is an example of error in PCG development by abnormal cell cycle
delayed mitotic arrest by germ cells in 129/Sv mice= more cancer
TGCT occur 10% of the time in ___ strain
129/Sv mouse strain
TGCT occur 30% of the time in ___ strain
129/terSv substrain
abnormal proliferation usually starts around what day in mice
E11-E12.5
how do tumors change their make up over time
fetal = undifferentiated= teratocarcinoma
5 days after birth= mix = teratocarcinoma
adults= differentiated= teratoma
mutations in what gene is responsible for high TGCTs in 129/terSv mice
Dnd1 (dead end homologue 1)
Dnd1
dead end homologue 1
RNA binding protein with a possible RNA editing function
delayed mitotic arrest
TGCT
Teratocarcinomas usually occur in ___ females
<20 year olds
Teratomas usually occur in ___ females
> 20 year olds
name of teratomas in older females
dermoid cyst
defects in ____ and ___ can lead to teratomas and teratocarcinomas in women
oocyte development
progression of meiosis
parthenogenetic activation within the ovary occurs in __ mice
LT/Sv
the phenomenon that oocytes exit from meiosis and enter the first cleavage division without fertilization
parthenogenetic activation
parthenogenetic activation is caused by
- hormonal disruption
2. disruption of meiosis
example of hormonal disruption in oocyte
LH (luteinizing hormone) increases but oocyte not realsed (ovulated) instead will go into mitosis with itself (daughter cell and polar body) 2 parts mom, 0 parts dad = teratoma
example of disruption of meiosis
failure to stop at meiosis I or failure to stop at Metaphase II
what is essential for maintaining metaphase II
Mos
Mos full name
c-mos proto-oncogene product
null-mos leads to
oocyte does not stop at metaphase II and mutates and develops teratoma
what indicates that DNA replication happened without sperm
BrDU