Cancer, Cell Regulation, and Mitosis

Characteristics of Cancer Cells vs Normal Cells

- Abnormal amount of nuclei result in cancerous cells - Less cytoplasm leads to cancerous cells - Less organized shaped and not structured shape are cancerous cells - Divide faster than normal cells >>> greater chance that the cell is in mitosis (mitosis looks different compared to normal cell mitosis). - Large mass of cancer cells >>> lead to tumors.

G2 Checkpoint

- Between the G2 and Mitosis phase - checks for cell size, DNA replication completeness, and DNA damage If errors or damage are detected, the cell will pause at the G2 checkpoint to allow for repairs. If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repair the damaged DNA. If the damage is irreparable, the cell may undergo apoptosis, or programmed cell death This self-destruction mechanism ensures that damaged DNA is not passed on to daughter cells and is important in preventing cancer.

How do we treat cancer?

- Surgery (removal of tumors) - Use of antibodies (attach to tumors and notify cell for removal) - Immunostimulants (stimulate the immune system's normal anti-tumor activity) - Chemotherapy - used to interfere with DNA replication, transcription, translation, and mitosis (but can still damage healthy cells) - Radiation (targeted to destroy tumor cells) - Stem cell transplants

Cancer

- any malignant growth or tumor caused by abnormal and uncontrolled cell division - cancer cells do not perform normal function - cancer cells divide repeatedly even though they are not needed - caused by gene mutations Cancer cells do not self destruct and continue to divide rapidly, producing millions of new cancerous cells.

G1 Checkpoint

- between the G1 and "S" phase - checks for nutrients, growth factors, cell size, and DNA damage - controls whether the cell will divide, delay division, or enter a resting stage (g0) Size: Is the cell large enough to divide? Nutrients:Does the cell have enough energy reserves or available nutrients to divide? Molecular signals: Is the cell receiving positive cues (such as growth factors) from neighbors? DNA integrity: Is any of the DNA damaged?

Metaphase Checkpoint

- transition from metaphase to anaphase (during mitosis phase) - checks for chromosome attachment to spindle at metaphase plate Here, the cell examines whether all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until all the chromosomes are firmly attached to at least two spindle fibers from opposite poles of the cell. Looks for "straggler" chromosomes that are in the wrong place (e.g., floating around in the cytoplasm) If a chromosome is misplaced, the cell will pause mitosis, allowing time for the spindle to capture the stray chromosome.

How is cancer related to the regulation of the cell cycle?

?

Mutagen

A factor which brings about a mutation is called a mutagen.

Carcinogen

Any agent that causes cancer is called a carcinogen and is described as carcinogenic. Carcinogens: Ionizing radiation - X Rays, UV light ■ Chemicals - nicotine from cigarettes ■ Mitosis stimulants - hormones ■ Virus infection - papilloma virus has been linked to cervical cancer (not a cause but a contributor).

Spindle Fibers

Attach to chromosomes and pull them towards different poles of the cell during the final phases of mitosis

Structure of Chromosome

Chromosomes are a more organized form of DNA generated by a cell prior to cell division and are Separate DNA molecules within an organism's genome Telomere is located on the ends

Why do we think the the form DNA takes when dividing; chromosomes, is important in controlling the successful completion of mitosis?

Chromosomes are much more organized

Damage to genes occur due to?

DNA Polymerase malfunction UV radiation damage Chemical Mutagens Viruses

What causes the gene mutations that result in cancer?

Environmental Factors Behavior Age Heredity

Internal Factors that Affect Cell Cycle

Enzymes Structural proteins Breakdown of nuclear membrane Attachment of kinetochores to spindle fibers

Why do cells divide?

For: Cellular Reproduction • Ex: binary fission in bacteria • Ex: Gamete production for sexual reproduction (meiosis, not mitosis) Cellular Growth Cellular Repair

What are the three major check points in the cell cycle?

G1 Checkpoint, G2 Checkpoint and Metaphase Check point

How do genes link to cancer and control the cell cycle?

Genes that are damaged when cancer occurs are genes that control different steps in the cell cycle. When the genes are damaged, it results in uncontrolled mitosis (cell growth) which results in the development of a tumor.

External Factors that Affect Cell Cycle

Growth factors Hormones Presence of nutrients Attachment to nearby cells Anchorage to extracellular structural proteins

Benign

Harmless; Benign tumors do not spread from their site of origin but can crowd out (squash) surrounding cells. Benign tumors are more likely to be treatable. Ex. brain tumor, warts.

Centrioles

Helps produce spindle fibers only in animal cells

What approach is being used with more recent cancer therapies?

Immunostimulants - stimulate the immune system's normal anti-tumor activity Monoclonal antibodies - attach to tumor cells and "flag" them for removal by immune system

G0 Phase

In G0, cells are metabolically functional, resting, but they are not ready to go into the "S" phase and begin preparing for cell division most human body cells spend most of their life span here some remain in G0 forever, such as non-dividing nerve and muscle cells For instance, it might conduct signals as a neuron (like the one in the drawing below) or store carbohydrates as a liver cell. G0 is a permanent state for some cells, while others may re-start division if they get the right signals.

Mutation

Is what causes all cancers Mutations that cause cancer are typically mutations in genes that produce proteins that control the cell cycle ■ Example: Oncogenes - "on switch" for mitosis ■ Example: Tumor Suppressor Genes - "off" switch for mitosis ■ Example: DNA repair genes A change in a gene or chromosome.

Malignant

Malignant tumors can spread from the original site through blood and lymph vessels and cause secondary tumors (metastasis). They interfere with neighboring cells and can block blood vessels, intestines, glands, lungs, etc.

Tumor Suppressor Genes

Normal genes produce proteins that prevent mitosis and triggers cell death in damaged cells Repairs DNA mistakes "off switch" for mitosis Mutated suppressor genes do not inhibit mitosis ■ cells divide excessively ■ damaged cells are not induced into apoptosis ■ Ex: p53 protein, BRCA1 and BRCA2

Development of Tumor

Occurs due to uncontrolled cell growth which was cause by damaged genes

Kinetochore

Portion of the chromosome centromere to which the mitotic spindle fibers attach.

Cell Division

Process by which a cell divides into two new daughter cells

Centrosome

Produce Spindle Fibers. Found close to the nucleus within the cytoplasm of cells.

Apoptosis

Programmed cell death A mechanism to remove old or damaged cells from the body ● Target cell is broken down within cell membrane to prevent release of enzymes to surrounding healthy cells ● Destroyed cell removed by macrophage (immune cell) Also plays a role in embryonic development and juvenile maturation

Chromatin

Relaxed form of DNA when not dividing

Significance of cancer gene research project

So we can know the difference of the characteristics of Cancerous cells vs Normal Cells

Role of Heredity

Some families are more susceptible to getting certain cancers ■ You can't inherit cancer but you may be more likely to develop it due to an inherited gene mutation ■ Ex: BRCA 1 & 2 and breast cancer

Chromosomes

The form of DNA takes for the process of mitosis

Why do cells divide at different rates? Why is it important that some cells divide quicker than others? Name some examples.

The function of each cell type determines its rate of reproduction. Ex. White Blood Cells divide every 2-5 days Skin Cells divide every 10-30 days Red Blood Cells divide every 4 months Fat Cells divide every 8 years Lens cells stay for lifetime Cerebral Cortex Cells stay for lifetime

Microtubules

Thick hollow tubes that make up the spindle fibers.

Why is early detection significant to cancer treatment?

To prevent metastasis

What type of gene is p53 and what is its role in the cell cycle?

Tumor Suppressor Gene "stop"

How does cancer specifically cause death?

Tumors interfere with neighboring cell and block blood vessels and nerves and interfere with normal functions. Also organ failure causes death.

Sister Chromatids

Two equal halves, are identical

Role of Aging

Why are older people more likely to develop cancer? ■ More years of exposure to carcinogens and mutagens ■ More rounds of DNA replication and mitosis (sources of errors) ■ Cellular repair slows down in older individuals

Does a mutated gene produce a protein product?

Yes

G1 Phase

also called the first gap phase, the cell grows physically larger, copies organelles, and makes the molecular building blocks it will need in later steps. reaches maturity

Proto-Oncogenes

are normal genes that stimulate the process of mitosis in response to extracellular signals Mutations convert them to oncogenes which overproduce and over-stimulate mitosis even in the absence of extracellular signals

Centromere

center where the sister chromatids are attached

G2 Phase

during this time, organelles & other materials required for cell division are made. This is the shortest stage of interphase.

Metastasis

is the medical term for cancer that spreads to a different part of the body from where it started transported by circulatory system (Stage 4 Cancer)

Histones

protein molecules around which DNA is tightly coiled in chromatin

Asters

refers to star like pattern of spindle fibers

Interphase

the cell grows and makes a copy of its DNA. Consists of the stages G1, S Phase, G2

Mitotic Phase

the cell separates its DNA into two sets and divides its cytoplasm, forming two new cells. involves two distinct division-related processes: mitosis and cytokinesis.

Mitosis

the nuclear DNA of the cell condenses into visible chromosomes and is pulled apart by the mitotic spindle, a specialized structure made out of microtubules. Mitosis takes place in four stages: prophase, metaphase, anaphase, and telophase.

"S" Phase

the period of activity during which DNA replication takes place (a complete copy is made of the cell's DNA so there are now 2 copies of all of the DNA).

Prophase

■ Chromatin condenses to form chromosomes ■ Centrioles move to opposite ends of cell (animal cells only) ■ Spindle fibers (protein strands) form from centrioles ■ Chromosome attach to spindle fibers at kinetochore ■ Nucleolus disappears ■ Nuclear membrane breaks down

How to prevent cancer?

■ Don't smoke! ■ Don't consume alcohol ■ Eat a healthy diet ■ Avoid sun exposure/wear sunscreen ■ Follow workplace safety guidelines ■ Follow medical recommendations for early detection

Cytokinesis

■ During cytokinesis, the cytoplasm divides & two distinct cells are formed. ■ The process occurs differently in animal & plant cells. ■ In animal cells, a cleavage furrow forms. ■ In plant cells, a cell plate develops. The new cells then go into interphase and the cycle continues for each of the newly formed cells.

Telophase

■ Final phase of mitosis ■ Chromosomes uncoil ■ Spindle breaks apart ■ Nuclear membrane forms ■ Nucleolus becomes visible

Metaphase

■ Shortest phase of mitosis ■ Microtubules of spindle fibers connect to chromosomes at kinetochore (region on chromosome that forms during mitosis) ■ Chromosomes line up across center (equator) of cell

Role of Behavior

■ Smoking & chewing tobacco ■ Alcohol consumption ■ Sunbathing ■ Poor diet ■ Workplace exposure

Anaphase

■ The centromeres split, separating sister chromatids ■ Chromosomes separate into two separate groups near poles of spindle (centrioles in animal cells) ■ Spindle fibers elongate, extending cell cytoplasm