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MDA-MB-453 is a
human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
cell line An immortalised cell line is a population of cells from a multicellular organism that would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
.


MDA-MB-453 Characteristics


History

The MDA-MB-453 cell cancer line was derived in 1976 from the pericardial effusion of a 48-year-old female who was suffering from a breast metastatic
adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
. The respective cells were collected at the Human Tumor Cell Bank.


Recommended media for growth

When growing the MDA-MB-453 cells, the recommended media for growth according to Lonza is a L-15 (Leibovitz). The medium does not have
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
,
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
,
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...
,
sodium bicarbonate Sodium bicarbonate ( IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda (or simply “bicarb” especially in the UK) is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cat ...
,
carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
, and
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
. The medium does contain
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
and
galactose Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...
. The L-15 medium was created in 1963 for the rapid growth of the MDA-MB-453 cell line. Also, it is recommended that the cells are treated with Fetal Bovine Serum. Fetal Bovine Serum increases cellular growth and plating efficiency.


Impacts/prevalence

In 2020, there was an estimated total of 684,996 deaths caused by breast cancer. Breast cancer is the fifth leading cause by death, so there is need of research and cell lines to understand how specific cancers work so accurate target therapies can be implemented.


Model for breast cancer

The cell line is a great model for breast cancer cells because the cells proliferate at a fast rate and is stimulated by androgens, but inhibited by progesterone, estrogen, and Her-2 receptors. The specific mutation that contributes to the cell cancer line is a glutamate to histidine change found on exon 7; more specifically, the amino acid 865. With the specific characteristics, the MDA-MB-453 cell cancer line is now classified as a Triple Negative Breast Cancer cell line model. One study suggests that the MDA-MB-453 cell line is not the best model for an apocrine breast cancer model. During the experiment, there was a mutation in the K-RAS gene that was not previously identified before. Also, there were structural abnormalities as shown on a Western Blot. Lastly, there were cell signaling differences that were not found in the samples. All of these characteristics are different from an apocrine breast cancer cell, which might lead to the idea that MDA-MB-453 cell line is not the best model. More specific differences between MDA-MB-453 and the apocrine carcinoma tissue sample differ in different features. They differ with the GCDFP-15 protein, HER-2/neu status, EGFR status, KRAS gene status, p16lnk4a protein, cyclin d1 protein, and polysomy 4 and 17. On the other hand, MDA-MB-453 cell line is a great model to understand
androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
and the
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...
in breast cancer. When the cell line was studied, there was androgen receptor expression and regulation. Androgen and the receptors in breast cancer have not been studied thoroughly, the cell line can accurately show how androgen and the receptor work within the specific breast tissue.


Natural antioxidants affect MDA-MB-453 cell line

There have been several recent studies that show different substances effect on MDA-MB-453 cells. All the different substances used had a common theme: to arrest cell proliferation and induce apoptosis. One of the substances is
quercetin Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor ...
, which is a natural antioxidant. The natural antioxidant increases the cells to enter the sub G1 phase of the cell cycle which will arrest the cell cycle and induce apoptosis. According to the data, quercetin has an anti-proliferation effect on MDA-MB-453 cells. The cells would undergo apoptosis, which concluded that quercetin could potentially have anticancer characteristics. Another substance is
kaempferol Kaempferol (3,4′,5,7-tetrahydroxyflavone) is a natural flavonol, a type of flavonoid, found in a variety of plants and plant-derived foods including kale, beans, tea, spinach, and broccoli. It is also found in propolis extracts. Kaempferol i ...
, which is also a natural antioxidant. The experiment was very similar to the quercetin experiment and have similar results: anti-proliferation effect on MDA-MB-453 cells. Another researched substance is
Fisetin Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It occurs in many plants where it serves as a yellow pigment A pigment is a powder used to add or alter color or change visual appearance. Pig ...
. Fisetin is found in fruits and vegetables and can induce apoptosis through the phosphatidylinositol 3-kinase /Akt signaling pathway and inactivation of the receptor. This is important with cancer research and further studies.


Cell biology

The androgen receptor is a ligand dependent transcription factor. In males, androgens are
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
and
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production o ...
, and has three domains: N-terminal transcription regulation, DNA binding, and the ligand binding. The biological implications of the androgen receptors are development in several systems, such as, reproductive, cardiovascular, neural, homeopathic, musculoskeletal, and immune. The signaling can also be involved with tumor development due to unregulated gene transcription. Since the receptor targets many different pathways and systems, it is a promising role medicine and new developments. When Heregulin (HRG), a secreted growth factor, is exposed to the MDM-MB-453 cells, a signal transduction pathway is induced. More specifically, the HRG beta 2 signals a
tyrosine phosphorylation Tyrosine phosphorylation is the addition of a phosphate () group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyrosine phos ...
. The HRG ligand activates a GTPase activating protein.


Epigenetic changes

Cowden Syndrome is a genetic disorder that makes an individual more susceptible to cancers. The cancers can be benign or malignant, and one of the more high-risk cancers are breast cancers. The specific mutation that contributes to this syndrome is a mutation in MDM-MB-453 cells, more specifically at codon 307 makes the cells more malignant that usual. The specific mutation is a glutamate to lysine substitution. The mutation is more susceptible to epigenetic changes, such as
ubiquitination Ubiquitin is a small (8.6  kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
, that effect localization and distribution from the cell. The study shows that this specific mutation in the MDM-MB-453 cells will make chemotherapy harder to target and the effects will not be as great.


References

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External links


Cellosaurus entry for MDA-MB-453
Human cell lines