REEXPRESSION OF INTERLEUKIN-1 IN HUMAN PAPILLOMAVIRUS-18 IMMORTALIZEDKERATINOCYTES INHIBITS THEIR TUMORIGENICITY IN NUDE-MICE

The ability to form tumors in nude mice developed spontaneously in the human papillomavirus (HPV)-18 immortalized keratinocyte cell line, 18 -11, and is shown here to be accompanied by a toss of interleukin 1 (I L-1) alpha and beta expression at both the RNA and protein level. In a ddition, a separate tumorigenic 18-11 derivative and two cervical carc inoma-derived cell lines, HeLa and Caski, were found to have significa ntly decreased or lost IL-1 alpha and IL-1 beta expression. Using retr oviral expression vectors, we re-established IL-1 expression in tumori genic 18-11 cells (18-11S3) in an effort to evaluate whether loss of I L-1 expression represented an important phenotypic change in the devel opment of tumorigenicity in these cells. IL-1-expressing 18-11S3 cells showed a range of tumorigenic potential, depending on the type and co mbination of IL-1 alpha and IL-1 beta expressed. Although 18-11S3 expr essing the precursor forms of both IL-1 alpha and IL-1 beta normally f ound in keratinocytes showed moderate inhibition of tumorigenicity, ot her IL-1-expressing lines showed complete inhibition of tumor formatio n. Co-injection of nontumorigenic, IL-1-expressing 18-11S3 with parent al 18-11S3 also inhibited tumor formation, These results suggest that maintenance of IL-1 expression may play an important role in preventin g progression to tumorigenicity in cervical carcinoma and other epithe lial cancers.