Discoveries – DNaseX and Apo10

Shortly after the discovery of the TKTL1 gene, I identified another gene of interest for cancer research whose base sequence was similar to the already known gene for the enzyme DNase I. The gene is located on the X chromosome and shows DNase enzyme activity. Since the gene is located on the X chromosome and the resulting protein has DNase enzyme activity, it was given the name DNaseX.

DNaseX in tumors

DNaseX has a special feature that makes it suitable as a universal tumor marker: In contrast to other DNases, whose expression decreases in the course of tumor development, the concentration of DNaseX enzyme in tumor cells increases. I have observed this phenomenon myself in CIN and cervical carcinoma cells.

What initially sounds paradoxical can be explained by the fact that DNaseX is increasingly formed in the tumor cell. However, by synthesizing special inhibitors, the tumor cell can suppress the enzyme activity of DNaseX and thus prevent the final apoptosis step – the cutting of the DNA¹.

DNaseX as universal tumor marker

The enrichment of DNaseX has been demonstrated in all premalignant and malignant tumor types studied so far². The detection of DNaseX overproduction can thus be interpreted as an indicator of impaired apoptosis and as an indication of the development of tumors in the body.
This is particularly well detectable when the so-called Apo10 epitope is detected. This characteristic part of the protein sequence of the DNaseX enzyme can be identified diagnostically with the monoclonal antibody Apo10 (DJ28D4) of the same name.

Apoptosis and DNases

The growth and survival of cells is strictly regulated. The targeted death of individual cells is essential for the development of our body as well as for the regeneration of tissues and the sorting out of cells with damaged genetic material. This programmed cell death – scientifically called apoptosis – triggers a chain reaction in the respective cell that ultimately activates various enzymes and thus initiates the enzymatic degradation of the cell from within. A final irreversible step in apoptosis is the cutting of DNA in the cell nucleus by enzymes known as DNases.

A fundamental common feature of all tumors is the disorder of apoptosis. Degenerate cells thus evade self-destruction, continue to grow and run the risk of further degeneration through further genetic damage (mutations) and increase in aggressiveness and malignancy. Research has shown that the DNA degradation in premalignant and malignant tumor cells is disturbed by DNases and apoptosis is thus blocked³. In cervical cancer cells, for example, it has been shown that the formation and activity of the enzyme DNase I decreases in the course of tumor development⁴.

Sources

Taper, H.S.: Altered deoxyribonuclease activity in cancer cells and its role in non-toxic adjuvant cancer therapy with mixed vitamins C and K3. Anticancer Res. 2008 Sep-Oct;28(5A):2727-32.

[PubMed]
Grimm, M. et al.: A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells. BMC Cancer. 2013 Dec 4;13:569.
[PubMed]
Taper, H.S.: Altered deoxyribonuclease activity in cancer cells and its role in non-toxic adjuvant cancer therapy with mixed vitamins C and K3. Anticancer Res. 2008 Sep-Oct;28(5A):2727-32.
[PubMed]
Zanotti, S., Fisseler-Eckhoff, A., Mannherz, H.G.: Changes in the topological expression of markers of differentiation and apoptosis in defined stages of human cervical dysplasia and carcinoma. Gynecol Oncol. 2003 Jun;89(3):376-84.
[PubMed]

Discoveries – DNaseX and Apo10

DNaseX in tumors

DNaseX as universal tumor marker

Apoptosis and DNases

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Dr. Johannes Coy