The molecular basis of cancer Flashcards
What is cancer?
Cancer is a multistep process requiring multiple mutations, so that it develops from multiple mutagenic events. Cancer is a group of genetic disease affecting fundamental aspects of cell functioning, including- DNA repair, the cell cycle, apoptosis, differentiation, cell migration, and cell-cell contact.
Caspases definiton
Caspases (protein enzymes) are a series of proteases (protein enzymes) that are responsible for initiating apoptosis, which is digesting intracellular components (of dead cells).
Caspases are a family of protease enzymes playing essential roles in programmed cell death.
What is carcinogen?
Any substance that causes cancer
What is the origin of cancer?
All cancer cells in tumors are clonal, which means that they originated from
a common ancestral cell that accumulated numerous specific mutations
(4 mutations, which lead to malignant cell)
The phenotypic response of cancer cells for each type of cell is the same or different? Provide an example.
The phenotypic response is different, because cancer may occur in different cells, which lead to the mutations in a wide variety of genes (different genes for each cell). For example: 2 breast cancers may be caused by very diverse set of mutations and present totally differently.
What are the functions of checkpoints in the cell cycle?
Checkpoints (proteins manage checkpoints) make sure that distortions don’t occur in the cell cycle
How can we get the Cancer of the cell from the cell cycle?
If one of the stages in the cell cycle is distorted, then we can get the mutation, which can lead to cancer.
Regulation of cell cycle progress is mediated by??
Regulation of cell cycle progress is mediated by cyclins (proteins) and cyclin-dependent kinases (CDKs - enzymes) that regulate synthesis (activate) and destruction (deactivate) of cyclin proteins by phosphorylation. (This is about all checkpoints, but G2/ M checkpoint is the last to make sure that DNA of the cell is undamaged). These 2 proteins manage checkpoints.
What is CDK-cyclin complex and it’s function of phosphorylation?
CDKs (cyclin-dependent kinases) only function when associated with Cyclins, which form CDK-cyclin complex. Phosphorylation is the addition of phosphate group by CDK-cyclin complex, which can activate or inactivate a protein
Enzymes definition
Enzymes are proteins (most of the time) that act as catalysts, which speed up the rate of the chemical reaction in the cell. When we see the end -ases, this means it’s an enzyme.
Apoptosis definition
If DNA damage is so severe —> apoptosis (Programmed cell Death)
Proto-oncogenes definition
Genes, whose products, under normal conditions promote cell growth and division (positive regulation of the cell cycle)
What are types of proteins encoded by proto-oncogenes? In other words, what are the 4 different groups of products that the proto-oncogene can make?
- Class I: Growth Factors
- Class II: Receptors for Growth Factors and Hormones
- Class III: Intracellular Signal Transducers that stimulate cell division
- Class IV: Nuclear Transcription Factors
Ras proteins definition
Ras proteins are made by ras genes and belong to proto-oncogenes family, which are frequently mutated in human cancers. They play an important role in many signaling networks (components of checkpoints) involved in cell cycle progression, and growth
What is the difference between normal cell and cancer cells in the Ras gene?
In a normal cell, Ras proteins alternate between inactive (off) & active (on) state by binding either GDP or GTP. When growth factor binds at receptor, the Ras gene product (protein) combines with GTP to promote proliferations (cell division) in normal cells.
In cancer cells, the RAS gene product (mutated) is locked into the state that it’s always going to bind GTP rather than GDP. As a result, we will have always proliferation even without growth factor.
What are Tumor Suppressor genes? Their function
Tumor Suppressor genes are genes whose product (proteins) block cell cycle progression at the checkpoints, which help to stop the progression of non-functional cells. (Negative regulation). Tumor Suppressor gene prevent cancer under normal conditions, stopping the progression of checkpoints followed by DNA repair or apoptosis.
What Tumor Suppressor genes do at the checkpoints?
Tumor Suppressor genes work at cell cycle checkpoints to initiate the process of apoptosis (destroy) or DNA repair. They both prevent from cancer to occur.
Retinoblastoma Tumor suppressor gene definition
Retinoblastoma Tumor suppressor is the kind of tumor suppressor gene, the loss or mutation of which contributes to development of many cancers including breast, bone, lung, and bladder (most prominent cancers).
What will happen after disruption/deletion of Rb gene
Inactivation of Rb protein (pRB is binded to E2F) –> uncontrolled cell proliferation (division) –> cancer
What is P53 tumor suppressor gene? It’s function.
P53 tumor suppressor gene is the kind of tumor suppressor gene, which encodes a nuclear protein (in the nucleus) that acts as a transcription factor (protein), repressing (stopping, followed by DNA repair or apoptosis) or stimulating transcription (go from DNA to mRNA) of the other genes (such as p21), the proteins of which manage the checkpoints.
P53 protein can influence the transcription of genes at the checkpoints only by repressing or stimulating other genes, such as p21.
The proteins of P53 tumor suppressor gene (which influence other genes, such as p21) are considered the guardian of the genome (protector of DNA, which work at 2 checkpoints - G1/S).
What is the function of activated p53 protein?
Activated p53 (protein) binds to DNA (and then transcription occurs) and activates expression of several genes including molecules (p21, which is protein) important in the G1/S transition in the cell cycle inhibiting the activity of the cell cycle. c. A mutated p53 gene is the most commonly mutated gene in the cell, which leads to cancers (mutated cell).
What is the normal p21 protein?
p21 (protein) is a Cdk inhibitor (protein p21 binds Cdk-cyclin complex, which inhibits kinase activity – the whole cdk-cyclin complex). It provides the normal function for the cell by stimulating or repressing transcription.
How ras proteins affect cell division in the cell cycle?
Once active, ras sends its signals (transduction signal) to the nucleus that regulates (repress or stimulate) transcription of genes, which proteins are involved in cell division.
