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(Embargoed for release Wednesday, June 3)
NYU Scientists Report Advances in Diagnosing, Understanding Bladder Cancer
Using a gene that only functions in bladder cells, scientists at New York University School of Medicine have developed the first transgenic animal model for bladder cancer and the first blood test for metastatic bladder cancer, providing valuable tools for better understanding the fifth most common cancer in the United States.
Xue-Ru Wu, M.D., Assistant Professor of Urology and Microbiology, and Tung-Tien Sun, Ph.D., Rudolf L. Baer Professor of Dermatology and Professor of Pharmacology and Urology, reported their findings in two studies presented June 3 in San Diego at the annual meeting of the American Urological Association. A third study also presented by Dr. Wu, shows that a protein abundant in urine may stop bacteria from sticking to the bladder, opening a new avenue for preventing urinary tract infections.
The researchers developed the transgenic animal model by introducing an oncogene into the bladder of mice. All the animals developed transitional cell carcinoma of the bladder, the form of the cancer that occurs in 90% of patients with bladder cancer.
"This is the first time we have an animal model for bladder cancer that can help us understand how mutations in certain genes can lead to this type of cancer," said Dr. Wu.
This year, there will be some 54,400 newly diagnosed cases of bladder cancer in the United States, and the cancer is expected to take the lives of 12,500 people, according to the American Cancer Society.
Until now, scientists have lacked an animal model for bladder cancer that they could use to understand how genetic alterations cause the cancer. In their study, Drs. Wu and Sun used a short piece of mouse DNA, called a promoter, to ferry the oncogene SV40 into cells lining the bladder of mice. The promoter itself was derived from a gene encoding a protein, called uroplakin II, found only in the bladder cells of mice. The gene was first described by Dr. Sun in 1995.
SV40, which is expressed as a viral protein, inactivates two tumor suppressor genes that are widely implicated in bladder cancer -- p53 and retinoblastoma. Mutations in these tumor suppressor genes are found in more than half of all bladder cancer patients.
Several lines of transgenic mice now have been created, said Dr. Wu. "These mice can be used for many purposes. For example, we can assess whether a mutation occurring in bladder cancer patients actually causes cancer. Then, perhaps we could find a way to block that mutation to prevent cancer."
In another study presented at the American Urological Association meeting, the NYU researchers used a gene for human uroplakin II to develop the first blood test for metastatic bladder cancer. In cancer that has spread beyond the bladder, cells from the bladder will be present in the blood.
In preliminary tests, the blood test detected uroplakins in 3 of 10 bladder cancer patients with metastatic bladder cancer. Now, Dr. Wu said the test is very specific, but must be further refined so that it is more sensitive.
In a third study presented at the meeting, Dr. Wu reported that a protein called tamm-horsfall (THP) inhibited the binding of a form of E. coli that commonly bind to uroplakins, enabling the bacteria to gain a foothold in the bladder and cause urinary tract infections. "This protein could serve as a major defense against urinary tract infections," said Dr. Wu.
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