- CHARLESTOWN, Mass. (UPI)
-- Researchers have identified perhaps one of the main controlling mechanisms
of cervical cancer.
-
- A human gene seems to regulate the genes of a virus that
has been associated with nearly all cases of cervical cancer -- the human
papilloma-virus.
-
- In malignant tumors in the human cervix, the activity
of a gene called Notch1 was very low or absent, researchers found. This
malfunction seems to allow the HPV to conduct its cancer-promoting enzyme
activity, leading to tumor growth.
-
- When the Notch1 gene is active and running at normal
speed, however, it can inhibit the growth of cervical cells infected with
HPV. Chemical signals from the Notch1 gene shut down production of two
proteins in the virus, called E6 and E7, that in turn interfere with the
cervical cells' ability to suppress tumor formation. This might be the
reason why, although many women can become infected with HPV, relatively
few develop cancer of the cervix.
-
- "In theory, if one were to devise ways of keeping
the expression of Notch1 elevated, that might be beneficial in the sense
it could block the invasive stage of carcino-genesis," researcher
G. Paolo Dotto, professor of dermatology at Harvard Medical School in Cambridge,
Mass., told United Press International.
-
- Dotto conducted much of the work at the Cutaneous Biology
Research Center at Massachusetts General Hospital in Charlestown.
-
- The Notch1 gene is found in all human cells and controls
a structure on the cells' surface that plays a key role in determining
how cells develop. Dotto and colleagues took human cervical tumor tissues
and evaluated the Notch1 gene's level of expression by using standard immunological
and tissue study methods.
-
- They also used an advanced technique called laser capture
microscopy to remove very specific regions of tumors -- even single cells.
Then, using RNA from the removed cells in a technique called real time
polymerase chain reaction, they could determine the level of Notch1's activity.
-
- They found whenever Notch1 expression slows down in the
cervical cells, it allows the viral E6 and E7 protein formation to accelerate,
thereby shutting down the chemical pathway by which cervical cells protect
themselves. Although E6 and E7 play an important role, other cell changes
probably are involved as well, researchers said.
-
- "This is a basic research paper," Debbie Saslow,
director of breast and gynecologic cancers at the American Cancer Society,
told UPI. "It has no direct immediate relevance to clinical care to
women who are interested in cervical cancer and getting screened."
-
- Saslow, who is a molecular biologist, added, "We
don't really understand the scientific reason behind why most people get
HPV as a transient infection but why so few of them actually get cancer."
-
- At least 70 percent of college-age women will test positive
for the virus at some time, she said.
-
- "It's an interesting piece of science," Steven
Rubin, chief of gynecological oncology at the University of Pennsylvania
in Philadelphia, told UPI. "It's basically one small piece in a complex
puzzle as to how the human papillomavirus causes cervical cancer."
-
- According to the National Cancer Institute, about 13,000
new cases of cervical cancer and about 5,000 deaths are reported in the
United States each year. HPV also causes genital warts in both men and
women.
-
- Part of the study was completed at the department of
pathology at Brigham and Women's Hospital in Boston.
-
- The research appears in the Sept. 1 issue of the journal
Genes and Development.
-
-
-
- Copyright © 2002 United Press International. All
rights reserved.
|
