Re-expression of interleukin 1 in human papillomavirus 18 immortalized keratinocytes 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 loss of interleukin 1 (IL-1) alpha and beta expression at both the RNA and protein level. In addition, a separate tumorigenic 18-11 derivative and two cervical carcinoma-derived cell lines, HeLa and Caski, were found to have significantly decreased or lost IL-1 alpha and IL-1 beta expression. Using retroviral expression vectors, we re-established IL-1 expression in tumorigenic 18-11 cells (18-11S3) in an effort to evaluate whether loss of IL-1 expression represented an important phenotypic change in the development of tumorigenicity in these cells. IL-1-expressing 18-11S3 cells showed a range of tumorigenic potential, depending on the type and combination of IL-1 alpha and IL-1 beta expressed. Although 18-11S3 expressing the precursor forms of both IL-1 alpha and IL-1 beta normally found in keratinocytes showed moderate inhibition of tumorigenicity, other IL-1-expressing lines showed complete inhibition of tumor formation. Co-injection of nontumorigenic, IL-1-expressing 18-11S3 with parental 18-11S3 also inhibited tumor formation. These results suggest that maintenance of IL-1 expression may play an important role in preventing progression to tumorigenicity in cervical carcinoma and other epithelial cancers.
Merrick
D T
DT
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104-2092, USA.
Winberg
G
G
McDougall
J K
JK
D000818:Animals; D015152:Blotting, Northern; D015197:Carcinogenicity Tests; D002461:Cell Line, Transformed / Q000737:chemistry / Q000502:physiology / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial; D027383:Papillomaviridae; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D002583:Uterine Cervical Neoplasms
D007375:Interleukin-1; D012333:RNA, Messenger