Loss of tumorigenic potential by human lung tumor cells in the presence of antisense RNA specific to the ectopically synthesized alpha subunit of human chorionic gonadotropin.
A clonal strain of human lung tumor cells in culture (ChaGo), derived from a bronchogenic carcinoma, synthesizes and secretes large amounts of alpha (alpha) and a comparatively lower level of beta (beta) subunit of the glycoprotein hormone, human chorionic gonadotropin (HCG). ChaGo cells lost their characteristic anchorage-independent growth phenotype in the presence of anti-alpha-HCG antibody. The effect of the antibody was partially reversed by addition of alpha-HCG to the culture medium. ChaGo cells were transfected with an expression vector (pRSV-anti-alpha-HCG), that directs synthesis of RNA complementary to alpha-HCG mRNA. The transfectants produced alpha-HCG antisense RNA which was associated with the reduced level of alpha-HCG. Transfectants also displayed several altered phenotypic properties, including altered morphology, less mitosis, reduced growth rate, loss of anchorage-independent growth, and loss of tumorigenicity in nude mice. Treatment of transfectants with 8,bromo-cAMP resulted in increased accumulation of alpha-HCG mRNA, no change in the level of alpha-HCG antisense RNA, release of the inhibition of [3H]thymidine incorporation, and restoration of anchorage-independent growth phenotype. The overexpression of c-myc, observed in ChaGo cells, was unaffected by the reduced level of alpha-HCG. These results suggest that ectopic synthesis of the alpha subunit of HCG plays a functional role in the transformation of these human lung cells.
Rivera
R T
RT
Laboratory of Molecular Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115.
Pasion
S G
SG
Wong
D T
DT
Fei
Y B
YB
Biswas
D K
DK
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division; D006063:Chorionic Gonadotropin / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000235:genetics; D007739:L Cells; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D012313:RNA / Q000494:pharmacology; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology
D006063:Chorionic Gonadotropin; D006657:Histones; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016372:RNA, Antisense; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012313:RNA