Genes & Cancer Pgs 1-16

Front 1

Stages of carcinoma development

Back 1

1) inital transfomed cell begin to proliferate giving rise to preneoplastic population
2)Cells that share mutations/characteristics progress to higher grades of dysplasia
3)lead to carcinoma in situ which is non-metastatic
4) additional changes lead to metastatic carcinoma
5) Share characteristics with precursor cells as well as unique characteristics of their own

Front 2

How often do mammalian cells divide

Back 2

about once every 24 hrs

Front 3

What are the 2 major steps that regulate division

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-S phase DNA synthesis
-M phase mitosis

Front 4

How does a cell enter the S phase

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S-phase is regulated by the S-phase promoting factor SPF

Front 5

What is SPF

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S-phase promoting factor which is composed of cyclin-dependent kinase (CdK) and cyclins

Front 6

What does CdK do

Back 6

phosphorylates the retinoblastoma tumor suppressor (Rb)

Front 7

What is Rb

Back 7

Retinoblastoma tumor suppressor. prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide.

Front 8

Unphosphorylated Rb

Back 8

Binds and inhibits transcription factor E2F which is necessary from the transcription of genes required for S-phase

Front 9

SPF CdK is inhibited by what

Back 9

binding of the CdK-interacting protein Pic1/WAF/p21

Front 10

What regulates entry into M-phase

Back 10

regulated by maturating promoting factor MPF.

Front 11

What is MPF

Back 11

composed of cyclin-dependent kinase, Cdc2, and cyclins

Front 12

What does Cdc2 do

Back 12

phosphorylates nuclear histone and lamin, which are events required for chromosome condensation and nuclear membrane breakdown during mitosis

Front 13

What is p53 tumor suppressor gene

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p53 protein is the guardian of the cell cycle, sensing cell abnormalities (like DNA damage) and shutting down cell division and/or inducing apoptosis. see pg P5 for visual aid

Front 14

Most human carcinomas form how

Back 14

mutations in the p53 tumor suppressor gene. Its one way tumor cells escape constraints on their cell division

Front 15

What is wild-type p53

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DNA binding protein and one of its function is to turn on the transcription of the Pic1/p21 gene

Front 16

How does pic1 protein work

Back 16

binds to the CdK in SPF and inhibits in kinase function, shutting down entry into the S-phase. see pg P5

Front 17

How does Mutant p53 act as a tumor marker

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it has a much lower degradation rate than wild-type protein, it therefore accumulates in tumor cells when it is mutated and elevated levels can be detected

Front 18

Carcinomas are derived from what cells

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Epithelia cells (kidney, pancreas, skin, etc.)

Front 19

Sarcomas are derived from what cells

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Mesodermal cells (blood, bone, muscle, nerve)

Front 20

Carcinomas are what % of human cancers

Back 20

90%

Front 21

Do the death rates of carcinomas increase with age

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Yes, they increase with age in a non-linear fashion. This suggests that carcinomas result from a multi-step process

Front 22

What does the carcinoma multi-step process involve

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series of DNA mutations which in combination result in more and more rapid cell division and tumor growth

Front 23

Human familial predisposition to colon carcinoma has revealed two genetic markers, what are they

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-fap (familial adenomatous polyposis) gene on chromosome 5q
-hnpcc (hereditary non-polyposis colon carcinoma) gene on chromosome 2p

Front 24

What does fap gene code for

Back 24

proteins associated with cell adhesion molecules

Front 25

What does hnpcc gene code for

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belong to a family of genes that are instrumental in proper DNA repair

Front 26

Can viruses be tumor-inducing agents

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yes

Front 27

Liver carcinoma's can be caused by what virus's

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Hep B/C

Front 28

Cervical carcinoma's can be caused by

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Papillomaviruses, which bind and inhibit cellular p53

Front 29

SV40 and polymavirus are small DNA viruses that can have a role in what

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possible roles in human cancer

Front 30

Retrovirus can cause

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adult form T-cell leukemia and Kaposi's sarcoma, a complication of AIDS

Front 31

How does Rous sarcoma virus cause tumors

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RSV is a retrovirus, contains src gene which is responsible for tumor formation, and "picks up" neighboring chromosomal genes (proto-oncogene) during the integration-repliation process, altered it in some fashion (converted to oncogene) and incorporated it into its genome

Front 32

c proto-oncogene form of src is located where

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cytoplasmic surface of the plasma membrane attached to myristate fatty acid

Front 33

What is the SRC protein

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tyrosine kinase that phosphorylates itself as well as other proteins

Front 34

What is the oncogene form of src (v) found in RSV virus missing

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coding region for the C-terminal region found in the intact proto-oncogene form

Front 35

What are the effects from v-SRC protein laking the ability to autoregulate its tyrosine kinase

Back 35

results in the unregulated kinase activity activating signal transduction in an unregulated manner.

Front 36

ALV is what

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Avian leukosis virus, activates proto-oncogenes from host chromosomal DNA

Front 37

ALV can have increased transcription of a cellular proto-oncogene called what

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myc

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myc does what

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This gene codes for a transcription factor that turns on genes required for cell growth. Elevated levels of this protein stimulates cell division and growth

Front 39

what mechanisms are there for converting proto-oncogenes to oncogenes

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nucleotide substitution, altered RNA polymerase promoters, chromosomal translocation, and gene amplification

Front 40

Chromosomal transloaction of the c-abl proto-oncogene causes what

Back 40

chronic myelogenous leukemia (CML)

Front 41

Epstein-Barr virus can lead to Burkitt's lymphoma how

Back 41

transloaction of the myc proto-oncogene to a chromosomal region of the overexpression

Front 42

Point mutation in the ras-oncogene G-proteins as well as in p53 are found in the majority of what

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human carcinomas and may be induced by carcinogens present in the environment

Front 43

How are chromosomes arms labeled

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long arm is designated q and the short arm is designated p

Front 44

What happens in CML (chronic myelogenous leukemia)

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the c-abl tryosine kinase gene on chromosome 9q is involved in a reciprocal translocation with the bcr region of chromosome 22qt (9q:22q). This generates an altered form of the c-ABL tyrosine kinase with altered activity in signal transduction leading to cell division

Front 45

What is the Philadelphia chromosome

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the reciprocal translocation between 9q and 22q generates a smaller than normal chromosome 22, which is diagnostic for CML