Herpesvirus 8 K1 Oncoprotein Directly Inhibits Fas-Mediated Cell Death

Human herpesvirus 8 (HHV-8) K1 oncoprotein binds directly to the Fas protein in tissue culture cells and blocks Fas-mediated cell death.

HHV-8 is associated with Kaposi sarcoma in humans and expression of the HHV-8 K1 oncoprotein leads to lymphoma in transgenic mice. Previous work suggested that K1 inhibits Fas-mediated cell death but the exact mechanism was unknown.

In the current study, Felipe Samaniego, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues transfected human cell lines with either a wild-type K1 gene or a K1 gene lacking an Ig domain, which is often involved in protein-protein interactions.

Fas activity was inhibited in cells that expressed wild-type K1 but not in cells expressing the Ig-deleted K1 mutant. Wild-type K1 protein expression protected mice from death due to stimulation of the Fas receptor, but the Ig-deleted mutant protein did not.

"The current results show that the HHV-8 protein K1 physically associates with Fas and thereby disrupts initiation of Fas-mediated apoptotic signaling induced by agonistic antibodies and [Fas ligand]," the authors conclude.

Contact: Scott Merville

Silencing HPV Genes Induces Cell Death in Oropharyngeal Cancer Cell Lines

Repression of human papillomavirus type 16 (HPV16) oncogenes E6 and E7 led to restoration of tumor suppressor gene activity and induced programmed cell death in oropharyngeal cancer cells grown in culture.

HPV16 is known to cause cervical cancer and has been associated with oropharyngeal cancers. However, mechanistic data showing a causal relationship between HPV16 and head and neck cancers has been lacking.

In the current study, Amanda Psyrri, Ph.D., of Yale University School of Medicine in New Haven, Conn., and colleagues introduced short hairpin RNAs (shRNAs) into HPV16-positive oropharyngeal cell lines. The shRNAs were designed either to interfere with HPV oncogenes E6 and E7 or to encode a scrambled control sequence.

Inhibition of the viral oncogenes resulted in renewed expression of endogenous tumor suppressor proteins p53 and pRB. Apoptosis increased in two oropharyngeal cancer cell lines from less than 13 percent in cells expressing the control shRNA to more than 70 percent in cells expressing the E6/E7-inhibiting shRNAs.

"These results, along with epidemiological and molecular pathology studies, con¬tribute to the establishment of a causal association between HPV and oropharyngeal cancer," the authors write.

Contact: Renee Gaudette

ABO Blood Groups May Affect Pancreatic Cancer Risk

Individuals with blood type O appear to have a lower risk of pancreatic cancer than individuals with blood types A, B, or AB, according to an analysis of two large independent cohort studies.

Genetic risk factors for sporadic pancreatic cancer are largely unknown. Previous studies have suggested that ABO blood types may be associated with several different malignancies, including pancreatic cancer.

In the current study, Brian Wolpin, M.D., of the Dana-Farber Cancer Institute in Boston, and colleagues examined the association between blood type and pancreatic cancer incidence in 107,503 individuals who participated in either the Nurses' Health Study or the Health Professional Follow-Up Study.

The age-adjusted incidence rate for participants with blood type O was 27 per 100,000 person-years, compared with 36 for individuals with blood type A, 41 for individuals with blood type AB, and 46 for individuals with blood type B.

"In two large, independent prospective cohorts, we observed a sta¬tistically significantly elevated risk for incident pancreatic cancer among participants with blood group antigens A or B compared with those with blood group O," the authors write. "Additional investigation is necessary to further confirm these findings and to determine the potential mechanisms by which ABO antigens may influence pancreatic cancer risk."

Contact: Bill Schaller

Also in the JNCI:

In Postmenopausal Women Systematic Estimation Of Breast Cancer Risk Appears Justified

Study Methods Influence Estimates Of Lead Time And Overdiagnosis In Prostate Cancer

Notes:

The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Visit the Journal online at jnci.oxfordjournals/.

Source: Caroline McNeil
Journal of the National Cancer Institute