Breast cancer research, in vitro model cell line study, MCF-7 human breast cancer cell line with it's details like history, importance, applications, Culture tips, a model responsible for ER targeted therapy etc.
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MCF-7: Human Breast Cancer Cell Line
1. MCF-7 : HUMAN BREAST CANCER
CELL LINE
Shaktiprasad Pradhan
M.Pharm, Ph.D*
Breast Cancer Researcher, UDPS
Utkal University, Bhubaneswar
Odisha, India
Cancer Research
3. MCF-7 : Human Breast Cancer Cell Line
Cell lines are in-vitro models for drug screening and
toxicity studies.
These are valuable tools to study problems of
clinical relevance, especially related to diseases,
screening, and studies of cell biology.
Cell lines have been used in vaccine & antibody
production, drug metabolism & cytotoxicity testing,
artificial tissue generation (artificial skin) &
synthesis of new therapeutics, study of gene
function etc.
MCF-7 is a very well known breast cancer cell line
of human origin.
4. MCF-7 cell was isolated from a pleural effusion of a
69 years old woman in 1970.
In 1973 Herbert Soule and his co-workers
established the MCF-7 human breast cancer cell line.
MCF is the acronym of “Michigan Cancer
Foundation” present in the Detroit city of USA where
the cell line was discovered & 7 represents Soule’s
seventh attempt for generating and establishing the
cell line .
Currently the Michigan Cancer Foundation (MCF) is
known as the Barbara Ann Karmanos Cancer
Institute (BAKCI), one of the 51 National Cancer
Institute designated comprehensive cancer treatment
and research centers in USA.
7. Globally MCF-7 is the most studied human breast
cancer cell line in compared to the other breast
cancer cell lines & more than 25,000 published
research reports on this cell line accounts for it.
Very well characterized for breast cancer
pathogenesis and therapy through reliable in vitro
assays.
It is a suitable model cell line for the anticancer
drug researchers investigating anti-breast cancer
drug molecules.
MCF-7 is the first hormone responsive human
breast cancer cell line.
8. MCF-7 is an excellent in vitro model for studying
the mechanism of tumor response to endocrine
therapy.
The MCF-7 human breast cancer cell expresses
androgen, progesterone along with glucocorticoid
receptors.
The extensively hormone sensitive nature of
MCF-7 breast cancer cell grounds for it’s
unanimously use in estrogen(ER) as well
progesterone receptor (ER) & hormone resistant
breast cancer in vitro experiments.
10. Originated from pleural effusion.
Primary tumor which is characterised as an
invasive breast ductal carcinoma.
Fairly large adherent cells & 20-25 micron is the
normal range of cell size.
MCF-7 cells are easy to propagate, commonly
slow-growing by nature having the doubling time
usually 30-40 hours.
Able to process estrogen in the form of estradiol via
estrogen receptors in the cell cytoplasm.
Both estrogen as well progesterone receptor
positive & and HER2 negative.
11. Proliferative response to both the ER & PR.
MCF-7 cells are sensitive to cytokeratin (CK).
Cannot have ERBB2 gene amplification.
Luminal epithelial phenotype.
Exhibit features of differentiated mammary epithelium
as they are positive for the epithelial markers.
Capable of forming domes when grown in vitro.
Tumorigenic in mice:
1. If engrafted subcutaneously into fat or mammary fat
pad only with estrogen supplementation.
2. If engrafted intraductally without estrogen
supplementation.
12. Growth of MCF-7 cells is stimulated significantly
by estrogens which is a broad area of cancer
research.
Growth and proliferation is inhibited by
angiogenesis, Omega-3 & 6 fatty acids (EPA,
DHA, AA).
Generate estrogen-dependent solid tumors and
can produce metastases to local and distant
lymph nodes.
MCF-7 cells contain a fraction of stem cells able
to generate clonal variability.
14. MCF-7 as a model of response for
ER targeted therapy
15. The hormone resistance studies have also been
basically instigated by the exercise of MCF-7
human breast cancer cell line.
MCF-7 cells are well-suited for antihormone
therapy resistance studies since they are
easily cultured and retain ER expression when
they were treated with such targeted therapy.
They express high levels of ER and become
hypersensitive to the estrogen stimulation, since
estrogen removal primarily slows the growth of
MCF-7 breast cancer cells markedly.
16. Various in-vitro studies using withdrawal or
frequent exposure of estrogen to MCF-7 breast
cancer cells lead to isolation of hormone resistant
different variants of MCF-7 cells, they may be
either ER positive or ER negative.
Several mechanisms of endocrine resistance
have been described including the over
expression or amplification of the hormone
receptors along with mutation which causes hyper
activation of the receptors.
This model is particularly valuable in preclinical
testing of antiestrogen therapies & identification of
mechanisms of resistance to such drugs.
18. MCF-7 cells are used extensively for in
vitro breast cancer studies.
Chiefly employed in the studies of hormonal
mechanism of action along with response and
resistance of different hormones.
MCF-7 cells are used for detecting the PI3K and
MAPK involvement.
Have been served as an important in vitro
model system to reveal other pathways.
Used in preclinical study models as an important
platform for the study of aromatase inhibitors.
20. MCF-7 human breast cancer cells may be seeded in
T75 flasks at a density of 1 million cells/flask in low
glucose Dulbecco’s modified Eagle’s medium
(DMEM) containing 10% fetal bovine serum (FBS),
2mM glutamine, 0.01 mg/ml Insulin and 1%
Penicillin/Streptomycin mix.
Then the MCF-7 cells should be cultured at 37˚C in
a 5% humidified CO2 incubator.
Renewal of the medium has to be performed twice
per week, while the MCF-7 cells should weekly be
passaged at a sub-cultivation in the ratio of 1:3.
No antibiotics should be added until its necessary or
the cell culture is clean in general.
21. An alternative cell culture medium for the MCF-7
human breast cancer cells would be, DMEM
supplemented with 10% FBS & antibiotics/
antimycotics.
Phenol red is advised for the culture of MCF-7 cell
line, as it is a weak estrogen and can bind to the
receptors on MCF-7 cells.
To successfully subculture MCF-7 cells, they need to
be brought into suspension.
Subculture only once a week, detach cells with
trypsin, then resuspend with DMEM, centrifuge
gently (3mins) & then resuspend the cell line
properly.
23. MCF-7 related
cell line
Description
MCF7/S0.5 Breast cancer cell line, Adapted to grow in low
serum media.
MCF7/182R-6 Breast cancer cell line, Fulvestrant resistant
MCF7/AnaR-4 Breast cancer cell line, Anastrozole resistant
MCF7/ExeR-4 Breast cancer cell line, Exemestane resistant
MCF7/LetR-1 Breast cancer cell line, Letrozole resistant
MCF7/TAMR-7 Breast cancer cell line, Tamoxifen resistant
24. References
1. Soule H.D., et al., A human cell line from a pleural effusion
derived from a breast carcinoma. J Natl Cancer Inst, 1973.
51(5):1409-16.
2. Lee A.V., et al., MCF-7 cells changing the course of breast
cancer research and care for 45 years. J Natl Cancer Inst,
2015. 107(7): 1-4.
3. European Collection of Authenticated Cell Cultures (ECACC).
4. Pradhan S., et al., Antiproliferation activity of Ocimum
gratissimum aqueous extract on human breast cancer MCF-7
cell line. WJPR, 2018. 7(9): 421-428.
5. Pradhan D., et al., Inhibition of proteasome activity by the
dietary flavonoid Quercetin associated with growth inhibition
in cultured breast cancer cells and xenografts. JYP, 2015. 7
(3): 225-233.