Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2Ld into a human colon cancer cell line (HCT).
Many human tumors, particularly those of epithelial origin, appear to express greatly reduced levels of major histocompatibility complex class I antigens on their surface. It has been previously reported that the class I gene H-2Ld, introduced into adenovirus type 12-transformed mouse cells, induces reversal of oncogenesis in immunocompetent BALB/c mice. We have tested the hypothesis that the H-2Ld gene, when transfected into HCT colon cancer cells, may alter their transformed phenotype. Two H-2Ld transfectants, HCT-Ii and HCT-If, were found to exhibit a markedly reduced-to-virtually suppressed ability to form colonies in soft agar in comparison to a transfectant (HCTh) carrying only the neomycin-resistance gene. We also compared the tumorigenicity of HCTh vs. HCT-If cells in two different strains of immunodeficient mice: nude (T-) and triple-deficient mutants (T-, NK-, B-). At 28 days postinjection of 10(7) and 10(6) cells, the size and growth rate of HCT-If tumors were greatly reduced compared to HCTh cells. Therefore, as assayed in immunodeficient animals, expression of the class I H-2Ld gene in HCT cells appears to correlate with partial suppression of the tumorigenic phenotype, suggesting that the expression of a transfected class I gene may by itself alter the phenotype of the recipient cell and that such phenotypic changes may be independent of the immune system.
Gattoni-Celli
S
S
Cancer Center, Massachusetts General Hospital, Boston.
Willett
C G
CG
Rhoads
D B
DB
Simon
B
B
Strauss
R M
RM
Kirsch
K
K
Isselbacher
K J
KJ
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005805:Genes, MHC Class I; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014162:Transfection; D014183:Transplantation, Heterologous