True/False Decide whether each of these statements is true or false, and then explain why. 1.

All the various cell types in a typical carcinoma, including fibroblasts, inflammation cells, and blood vessels, evolve from the cancer cell population. FA !" #fibroblast, inflammation cells, and blood vessels are normal cells, not evolved from cancer cell although they are in contact with tumor cells$ %. &n the cellular regulatory pathways that control cell growth and proliferation, the products of oncogenes are stimulatory components and the products of tumor suppressor genes are inhibitory components. T'(" #because the oncogene are stimulatory component, tumor suppressor gene is inhibitory component$ ). &t is clear from studies in mice that mutagenic activation of a single oncogene is sufficient to convert a normal cell into a cancer cell. FA !" #single oncogene is not sufficient to convert normal cell into cancer cell. !till need cells in some tissue that show enhanced proliferation. *ccasionally these cells will undergo changes into cancer cell$ +. The loss of p,) protein ma-es cancer cells much less sensitive to irradiation and to many anticancer drugs, which would otherwise destroy tumors by inducing proliferating cells to either stop dividing or undergo apoptosis. T'(" #p,) cause the cell to commit suicide by apoptosis$ ,. .any carcinomas show both chromosomal instability and defective mismatch repair. FA !" #"ither one can be seen in carcinomas$ /roblems 1. "pidemiological studies can provide suggestive lin-s between environmental factors and cancer. For example, as shown in Figure, the curve for deaths due to lung cancer in the (! parallels the curve for per capita cigarette consumption. 0owever, the curve for lung cancer is displaced by some %, years from that for cigarette smo-ing. 1hat do you suppose is the basis for this delay2 1hat would you say to your uncle, who insists that people who smo-e are inherently more cancer prone and that lung cancer really has nothing to do with cigarettes. The delay is because time is needed to accumulate sufficient number of changes so that it become cancerous.

%. Rb is one example of a category of antiproliferative genes in humans. Typically, when both copies of such genes are lost, cancers develop. Do you suppose that cancer could be eradicated if the tumor suppressor genes such as Rb could be expressed at abnormally high levels in all human cells2 1hat would be the effect on the human2 "xplain your answers. 3oth normal cell and cancer cell cannot proliferate. Die la. ). *verexpression of the .yc protein is a common feature of many types of cancer cells, contributing to their excessive cell growth and proliferation. 3y contrast, when .yc is overexpressed in most normal cells, the result is not excessive proliferation, but cell4cyle arrest or apoptosis. 0ow do you suppose that overexpression of .yc can have such different outcomes in normal cells and cancer cells2 &n normal cell, the chec-point normally disable overexpression of cells. 3ut not in cancer cell. +. Discuss the following molecular mechanisms of cancer54 a$ !ingle point mutation of 0er% and its overexpression A single point mutation converts the 0er% receptor into the neu oncogene in murine cancers .any human breast cancers overexpress an otherwise normal 0er% receptor this results from gene amplification #locali6ed re4duplication of D7A segment containing the proto4oncogene$ cells are therefore stimulated to proliferate in the presence of very low concentrations of hormones li-e "8F monoclonal Ab against 0er% has proven to effectively -ill cancer cells without affecting cells that express moderate levels of 0er% b$ 94src 7ormal src -inase coded for by the c4src gene is a protein containing sh%, sh) and pt- domains. :inase activity is switched of by phosphorylation of the tyrosine residue at position ,%;

!ubse<uent hydrolysis of phosphotyrosine ,%; normally activates c4src &n src oncoproteins the tyrosine ,%; is missing or altered leading to constitutive -inase activity c$ /T"7 /T"7 phosphatase is deleted in many types of advanced human cancers /T"7 has broad specificity and can de4phosphorylate phosphor4serine, threonine and tyrosine residues =ells lac-ing /T"7 have elevated levels of phosphatidylinositol ),+,, triphosphate and protein -inase 3, which both act to prevent apoptosis Deletion of /T"7 reduces apoptosis d$ c4.yc c4.yc is a transcription factor that switches on the expression of other genes. 1hen cells are stimulated to divide, there is a rapid increase in c4.yc '7A 3ur-itt>s lymphoma is a 34cell tumour in which the c4.yc gene is translocated to a site near the antibody heavy chain genes #&g0$ The &g0 chain gene is expressed at high levels in 34cells =4.yc is now placed under the control of the &g0 enhancer Abnormally high levels of c4.yc protein is constitutively produced 8enes down4stream in the signal cascade are activated inappropriately and 34cells can become transformed e$ p,) D7A damage sensing #chec-point$ protein, in which cell monitors D7Adamage during the cell cycle /revent the phosphorylation of 'b, -eeping 'b in an inactive state unable to act upon "%F, thus halting the cell cycle until D7A repair is effected 0as effect through a range of different cyclin/=D: complexes, hence can act at any point throughout the cell cycle .inimal repairable D7A damage induces the p,) mediated arrest to allow D7A repair and avoid accumulation of mutations !erious D7A damage that cannot be repaired triggers p,) dependent cell death by apoptosis 3en6o#a$pyrene causes p,) mutations 0/9 protein "? is also -nown to be able to inhibit p,) f$ 'b 'b controls the expression of genes that commit cells that are in the restriction point to enter !4 phase &n early 81 phase unphosphorylated 'b prevents the D7A binding activity of the "%F transcription factors and represses the advance of the cell cycle

=lose to the restriction point the 'b protein is phosphorylated. This allows "%F transcription factor to activate its downstream targets and the cell cycle progresses g$ Ataxia Telangiectasia 'are autosomal recessive disease caused by mutations in the AT. gene (nsteady posture #ataxia$, due to neurological abnormalities, vasodilation #telangiectasia$ AT. protein is constitutively expressed during cell cycle and has a chec-point function to monitor D7A damage and determine whether p,) mediated growth arrest and D7A repair or p,) mediated apoptosis occur h$ .utation in A/= #Adenomatous /olyposis =oli$ gene Familial Adenomatous /olyposis #FA/$ is caused by inactivating germline mutations in A/= gene A/= promotes degradation of @4catenin accumulates and activates transcription factors resulting in deregulated cell growth and cancer

,. "xplain how the tumour cells trigger angiogenesis and why angiogenesis is re<uired for the growth of tumour cells. Angiogenesis is the formation of new blood vessels =apillaries extend into all tissues of the body providing blood supply 7ormally capillaries do not increase in si6e or number as endothelial cells lining capillaries do not divide, unless due to exception such asA 4 7ormal5 menstruation, tissue repair 4 Abnormal5 cancer 0ow Tumor cells can produce proteins that promote new capillary growth &t may mobili6e angiogenic proteins found in nearby tissue &t may also prompt other cells such as macrophage to produce angiogenic proteins Tumor cells produce % types of proteins 4 *ne stimulates angiogenesis, one inhibits angiogenesis 4 The balance between these determine if tumor can switch on angiogenesis 1hy A developing tumor needs a blood supply, without which it will be small and harmless #si6e restriction due to lac- of readily available nutrients, growth factors and oxygen$ After months/years, tumor cells can trigger angiogenesis and become an invasive, metastatic carcinoma

Angiogenesis is critical step in transition of tumour from a small cluster of cells to large malignant growth

?. 1hat is the function of the telomerase and discuss the use of inhibitor telomerase in the treatment of cancer. Telomerase maintains the telomere length by replacing telomere se<uences that are trimmed away at each !4phase of the cell cycle This result in the tumor cell does not sense approaching senescence and becomes immortal Telomerase inhibitor can be used to treat cancer by #either one, not sure$ 4 &nhibit the expression of telomerase gene o Telomerase is not expressed o Telomere4cap se<uences are trimmed away, will not be replaced and become short o =ell senescence is induced once they shrin- below a certain length 4 &nhibit the action of telomerase o 3ind to telomerase and inactivate the en6yme o Telomere4cap se<uences are trimmed away, will not be replaced and become short o =ell senescence is induced once they shrin- below a certain length

;. Discuss factors which cause cancer. DietA 0igh fat, additives, high calorie 4 Animal #saturated fat$ and read meat5 colorectal cancer 4 0igh salt inta-e5 stomach cancer 4 *vereat, excessive childhood growth in girls leads to early menstruation5 breast cancer 'adiationA natural, man4made, 4 !un high fre<uency (943 rays damage D7A5 s-in cancer #melanoma$ 4 'adon gas prolonged inhalation5 lung caner 4 =ellular phones5 brain cancer =arcinogen in wor-place 4 "thidium bromide 4 =ancer of lung, s-in and bladder, leu-emia

.edication 4 &mmunosuppresive drug5 lymphoma 4 8rowth hormone5 leu-emia 4 Fertility drugs5 ovarian cancer 4 *ral contraceptive5 liver tumors and breast cancer 4 =holesterol reducing drugs5 colon cancer &nfectious micro4organism 4 0/9 type 1?,1B5 cervical cancer 4 0epatitis 3, =5 liver cancer 4 "395 lymphoma, stomach cancer, nasopharyngeal cancer 4 0&95 :aposi>s sarcoma, lymphoma 4 0elicobater pylori5 stomach cancer /olution 4 "nvironmental pollution of air, water and soil5 lung cancer 4 Diesel "xhaust 4 /esticides such as DDT 4 Cenoestrogens5 breast cancer 'eproductive and gynaecological 4 "arly age menstruation, late age first pregnancy, late age menopause5 breast cancer !ocio4economic 4 ower socio4economic status lin-ed to smo-ing and alcohol5 mouth, lung, stomach, cervical, liver cancer 4 0igh socio4economic status5 breast, prostate cancer &nherited genetic mutation 4 8ermline recessive tumor suppressor genes