Thanks dear really for your help

You can not classify it as pro- or antiapoptotic. It's all a question of mutated or wild type p53... It's mutated in cancer cells and wild type (norma) is considered as a proapoptotic or proliferative protein in healthy (when the cell is too damaged it initiates apoptosis, when everything is OK - DNA repair). Bcl-2 is considered as a an antiapoptotic protein, but I think You should search for more information in reliable web-sources, wikipedia.org for instance.

So the mutated p53 in the cancer cell can appear as increase amount in the immunohistocemistry stained slides

i mean the induction with DMBA (carcinogen) cause the p53 conversion to mutated type and appear in the slides with increase amount not decreased

In some cancer cells it can appear but its useless in apoptosis induction (thats why its very important to differ those two type, which is a hard task). But it won't appear in big amount, I even would say, very small amounts. The other thing is that this protein cannot be called pro- or antiapoptotic. It decides wheather the cell will proliferate or die via a apoptosis pathway... That's why its important that this protein works correctly (the mutated form work in a inapropriate way). In my oppinion its too much talking about p53, as this protein is overrated, there are other important proteins in the ATM/ATR pathway, that can even turn the p53 effect in the opposit way... p21, WAF1, Wee1, E2F, Rb... too many to mention :)

I'm not very that knowleged in p53 pathways, but if You like, I would send You my review article about giant cancer cells and p53 defficiency. I've observed that they have an increase p53 signal, thus they survive and give rise to daugther cells... so the p53 protein actually does not kill them. Yes, it's an important protein, but somehow cancer cells escape cell death, even when p53 is active...

A lot of thanks dear and i will contact you

Dear Fathi, p53 is on of the more known anti-oncogenes that helps in protecting the cells against tumorigenesis by several pathways, one of which is down regulation of bcl2 an anti-apoptotic regulatory gene located in mitochondria.. In case DNA of the cell is damaged or mutated but is reparable, p53 through target proteins helps in cell cycle arrest in G1 phase, so as to allow repair of the damaged DNA by DNA repair machinery of the cell. Whereas, if the DNA due to any insult is irreparably damaged or mutated, p53 activates the pro-apoptotic gene Bax, so thar the cell with damaged DNA is made to undergo apoptosis. In significant no. of cases of cancer of the breast and colon and others, p53 mutations have been detected, thus the cells with mutant p53 may show increased replicative potential than others. In summary, increased expression of p53(muatant type) and decreased expression of bcl2 indicate higher cancer risk.

Thanks dear Dr Naresh you really clearing that. I got what i wont , but now in the just treated animals with the natural products and thy give me the positive p53 expression, so this is the p53 normal not mutated

On the other hand the group which was applied for DMBA (carcinogen) have also positive p53 but mutated >>>> is that clear and wright to differentiate between the two types of p53?

I mean how can i confirm the mutated p53, is just due to i used that carcinogen?

Gear Fathi, normally p53 should not be expressed in cancer cells or in other words it is down-regulated in cancer. However, if it is expressed in transformed or cancer cells, it ought to be mutant form, which does not deliver normal anti-proliferative influence. Hope that answers your query.

Great , so if i have two slides of the group of cancer :

1. with negative p53 >>>> so its the normal type and it decreased normally due to cancer

2. with positive p53 >>>> so its mutated one and increased due to cancer.

is that can be expressed as i said?

and tanks for your informing me its great clear for me now

Fathi, P53 is a tumor suprresor gene and BCL-2 is an anti-apoptotic genes.Increase in BCl2 level decreases the level of P53. Therefore if you treat any cancer with any sort of drug, it will normally upregulate p53 , and thereby downregulating BCL2

Now its clear from all thanks dears really you are very helpful

Normally activation of p53 can result in cell cycle arrest, presumably to allow for DNA repair before replication or mitosis. In some cell types, however, p53 activation results in apoptosis as means of eliminating severely damaged cells. The final outcome of p53 activation depends on many factors, and is mediated largely through the action of downstream effector genes transactivated by p53.

p53 is shown to be either non-functional or mutated in most human cancers. The most common anomaly of p53 in human cancers is mutation of the p53 gene. Functional p53 provides a protective mechanism against tumor growth and a loss of p53 function is a key step in the neoplastic cascade. In addition, the function of p53 is critical to the success of many cancer treatments since radiation and chemotherapy act in part by triggering cell suicide in response to DNA damage. A successful response to therapy is greatly reduced in tumors where mutant p53 is present, and these tumors are often very difficult to treat.

BCL-2 is an anti-apoptotic protein located on the outer mitochondrial membrane. Anti-apoptotic members of the BCl-2 family are in the mitochondria and pro-apoptotic members are in the cytoplasm, but they translocate to mitochondrial upon receipt of apoptotic signals.