Dr. Tak Mak and scientists at The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital have discovered the role of two "cousins" in the genetic family tree of cancer development.

The findings, published online in the journal Genes and Development, plant the seed for a critical new branch of scientific inquiry, says Dr. Mak, principal investigator. Dr. Mak, Director of The Campbell Family Institute is also a Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.

The cousins are proteins related to the gene p53 family - the patriarch known for two decades to be the master gatekeeper that controls all cancer development. When gene p53 is defective, it loses its ability to regulate healthy cells and suppress cancer.

"Until now, we thought these cousins (TAp73 protein isoforms) were not involved in cancer. Our results prove that they are. This is fundamental to understanding every human cancer and furthering the science."

In the lab, Dr. Mak and his team challenged traditional thinking about the role of these proteins. "Before, scientists studied only whether these proteins were present or absent. We decided to study how they interact with each other and discovered that they actually have a split personality. When we turn one ‘on' or ‘off', the other changes behavior and becomes part of the cancer-causing process. The key is understanding the ratio of the interaction."

"The next step is to understand how the ratio affects cell division that leads to human cancer," says Dr. Mak, whose work was supported by the Canadian Institutes for Health Research.

About Cancer

Cancer (medical term: malignant neoplasm) is the general name for a group of more than 100 diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer cells can spread to other parts of the body through the blood and lymph systems. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer that begins in basal cells of the skin is called basal cell carcinoma.

• Carcinoma - a cancer which is derived from the lining cells, or epithelium, of an organ. There are 4 major types of epithelium in the body (Glandular, squamous, transitional, and pseudostratified). Some types are only found in a few select organs such as the lung (pseudostratified) or urinary bladder (transitional).  Carcinomas can arise from any of these epithelial types. For example, breast carcinoma is most commonly derived from the lining cells of the milk producing glands. A carcinoma with a glandular growth pattern is an adenocarcinoma.  Common adenocarcinomas include prostate, colon, and breast.  A carcinoma with a growth pattern resembling the squamous lining cells is termed a squamous cell carcinoma.  Common squamous cell carcinomas are found in the esophagus and skin.  However, any of these organs may have either type of carcinoma arising from it, although these latter diagnoses are exceedingly rare.
• Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
• Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
• Lymphoma - a cancer derived from the white blood cells that are present in the lymphoid tissues of the body.  These sites most commonly include the lymph nodes and spleen. However, lymphomas may arise from any organ and body site.
• Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking, limiting time in the sun, being physically active, and eating a better diet. Half of all men and one-third of all women in the US will develop cancer during their lifetimes.

• Growing Older
• Family history of cancer
• Poor diet, lack of physical activity, or being overweight
• Alcohol
  

About Breast Cancer

• Ductal carcinoma in situ (DCIS): This is the most common type of non-invasive breast cancer (85 - 90% of all cases). DCIS means that the cancer is only in the ducts. It has not spread through the walls of the ducts into the tissue of the breast. Nearly all women with cancer at this stage can be cured. Often the best way to find DCIS early is with a mammogram.
• Lobular carcinoma in situ (LCIS): This condition which occurs in approximately 8% of all cases, begins in the milk-making glands but does not go through the wall of the lobules. Although not a true cancer, having LCIS increases a woman's risk of getting cancer later. For this reason, it's important that women with LCIS to follow the screening guidelines for breast cancer.

• Inflammatory breast cancer (IBC): This uncommon type of invasive breast cancer accounts for about 1% to 3% of all breast cancers. Usually there is no single lump or tumor. Instead, inflammatory breast cancer (IBC) makes the skin of the breast look red and feel warm. It also gives the skin a thick, pitted appearance that looks a lot like an orange peel. Doctors now know that these changes are not caused by inflammation or infection, but by cancer cells blocking lymph vessels in the skin. The breast may become larger, firmer, tender, or itchy. IBC is often mistaken for an infection in its early stages. Because there is no defined lump, it may not appear on a mammogram, which may make it even harder to catch it early. It usually has a higher chance of spreading and a worse outlook than invasive ductal or lobular cancer.
• Paget's disease of the nipple. Paget's disease of the nipple or breast is a rare type of breast cancer, which can occur in women and men. It shows up in and around the nipple, and usually signals the presence of breast cancer beneath the skin. Most cases are found in menopausal women, but can also appear in women that are as young as 20.  Early stages symptoms include redness, scaly and flaky, and  mild irritation of  nipple skin. Advanced stages may include: tingling in nipple skin, very sensitive skin on the nipple, burning or painful nipple skin, ooze or bloody discharge from the nipple (not milk), itchiness that doesn't respond to creams, nipple retraction (pulls into the breast), scaly rash on areola skin, and/or breast lump beneath the affected skin.

• a lump or a thickening in the breast or in the armpit. Note Most breast lumps are benign (be-nine); that is, they are not cancer. Benign breast tumors are abnormal growths, but they do not spread outside of the breast and they are not life threatening. But some benign breast lumps can increase a woman's risk of getting breast cancer. Most lumps turn out to be caused by fibrocystic (fi-bro-sis-tik) changes. Cysts are fluid-filled sacs. Fibrosis is the formation of scar-like tissue. Such changes can cause breast swelling and pain. The breasts may feel lumpy, and sometimes there is a clear or slightly cloudy nipple discharge.
• a change of size or shape of the mature breast
• fluid (not milk) leaking from the nipple
• a change of size or shape of the nipple
• a change of color or texture of the nipple or the areola, or of the skin of the breast itself (dimples, puckers, rash)
• a discharge from the breast
  

About Dr. Tak Mak

Dr. Tak Mak is a pre-eminent Canadian scientist and internationally acclaimed immunologist, renowned for his 1984 discovery of cloning the human T-cell receptor. His discoveries have made an enormous contribution to the understanding of immunity and especially as it relates to cancer and HIV/AIDS. Dr. Mak, Director of The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital, University Health Network, has published more than 600 articles and received more than 3,000 citations in leading scientific journals. He is also Professor, University of Toronto, in the Departments of Medical Biophysics and Immunology.

His honours include the Gairdner Foundation International Award, the Emil von Behring Prize, the E.W.R Steacie Prize, and the General Motors Research Foundation Alfred P. Sloan Prize. Dr. Mak is an Officer of the Order of Canada, a Member of the Order of Ontario and recipient of the Premier's Summit Award, and a Fellow of the Royal Society of Canada and the Royal Society of London.

About The Campbell Family Institute for Breast Cancer Research

The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital brings together an elite team of cancer researchers, scientists, clinicians and staff dedicated to the ultimate goal of conquering breast cancer by leveraging basic, translational and clinical research into dramatic breast cancer breakthroughs. http://www.campbellfamilyinstitute.com/

About Princess Margaret Hospital

Princess Margaret Hospital and its research arm Ontario Cancer Institute -- which includes The Campbell Family Cancer Research Institute and The Campbell Family Institute for Breast Cancer Research -- have achieved an international reputation as global leaders in the fight against cancer. Princess Margaret Hospital is a member of University Health Network, which also includes Toronto General Hospital and Toronto Western Hospital. All three are research hospitals affiliated with the University of Toronto. http://www.uhn.on.ca/