The p53 Tumor Suppressor Gene and Apoptosis

The image at left links to the National Center for Biology Information (NCBI) article on the p53 gene. Click on the image to go! A new browser window will open. Come back here to read about p53 and prostate cancer.

A record of the DNA coding of p53 derived from human male prostate LNCaP cell line is at NCBI Human Genome Project. The DNA sequence is at the bottom of the screen beneath a long list of names of researchers who helped decode it. Other views of this same information are available on the site.

What does p53 have to do with prostate cancer?

Apoptosis-regulating genes are believed to play an important role in the development and progression of prostate cancer. They are viewed as a potential target for future treatment strategies.

p53, a tumor suppressor gene, helps regulate the cell cycle. It plays a key role in ensuring that damaged cells are destroyed by apoptosis (programmed cell death). p53 is the most commonly mutated gene associated with cancer.

Normally, if anything damages the DNA (genetic code) in the body's cells, protein p53 puts a brake on the cell cycle. Cellular repair systems set to work and, if necessary, get rid of the damaged cells by apoptosis (a form of cell suicide).

p53's job is cell cycle arrest. But if p53 itself has mutated and no longer works properly, proliferation of damaged cells goes unchecked. Cancer and spread of cancer can occur.

Efforts to find therapies that will stimulate apoptosis despite p53 malfunction are underway.

What difference does it make to already diagnosed patients to know about genetic factors in prostate cancer?

Patients with more advanced disease may wish to know something about new therapies involving genetic targeting especially if these look promising in Phase I trials and are likely to become available in Phase II and Phase III trials. Even if the therapies are expected in the long run to benefit early-stage patients most, some benefit may occur during the trial. At the same time, a fair idea of risks and benefits of novel therapies in trials can help a patient avoid wasting time if standard treatment offers higher chance of solid benefit.

Patients with localized prostate cancer may wish to seek genetic information to help them decide (1) whether they need aggressive treatment; (2) what treatment options are best for them; and (3) what treatment outcomes can be expected.

This does not change basic needs. A patient who chooses to have surgery needs an accurate evaluation of the pathological stage of the cancer once the gland has been removed. This is considered to be "the most powerful predictor of outcome following radical prostatectomy, and its prediction (organ-confined vs. seminal vesicle or lymph node involvement) is aided by knowledge of clinical stage, Gleason score, and PSA level."

But in addition the patient may wish to have information about genetic markers. C. A. Pettaway says: "Several novel markers of biological aggressiveness are associated with critical steps of the metastatic cascade (growth, invasion, angiogenesis, and resistance to apoptosis) and include the p53 tumor suppressor gene, the bcl-2 proto-oncogene, markers of increased proliferation (Ki-67), apoptosis, and angiogenesis (microvessel density)." For a patient who has clinically localized surgery prostate cancer, Pettaway says, these markers "provide a 'ballpark' estimate of outcome."

This article draws in part on Tech Urol 1998 Mar;4(1):35-42 Prognostic markers in clinically localized prostate cancer. Pettaway CA, Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.