[Studies on the reduction of malignant phenotypes in a highly metastatic human lung carcinoma--correlated changes of intercellular communication, cytoskeletons, oncogenes and antioncogene].
Human lung giant cell carcinoma cell line PG is characterized by its highly metastatic (100%) behavior in nude mice. When compared with cultured normal human fetal lung cells, PG cells were deficient in gap junctional intercellular communication (GJIC) function as detected by Scrape Loading and Dye Transfer method. Tubulin immunofluorescent and rhodamine-phalloidin staining revealed disorganization of microtubules and disruption of stress fibers with appearance of reorganized F-actin-bodies in PG cells. Northern or dot blot hybridization results showed that PG expressed high levels of c-myc and c-Ha-ras oncogenes and low level of antioncogene P53. Southern hybridization demonstrated that PG also exhibited c-myc gene amplification. When PG was treated with calmodulin antagonist calmidazolium (CDZ, 100-200nmol/L) or a Chinese medicinal mixture L2 (3-13mg/ml), cell proliferation was inhibited, GJIC function restored, and microtubule network recovered. But only L2 was efficient in (1) improving the stress fiber organization, (2) inhibiting the colony formation in soft agar, (3) reduction of c-myc amplification and expression, and (4) up-regulation of P53 mRNA level. The correlation between markers of malignant phenotypes and the reversion of PG cells is discussed.
Zhang
Z Q
ZQ
Beijing Institute for Cancer Research.
Lin
Z X
ZX
Lu
Y Y
YY
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D018286:Carcinoma, Giant Cell / Q000235:genetics / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005784:Gene Amplification; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002147:Calmodulin; D004365:Drugs, Chinese Herbal; D007093:Imidazoles; C031938:calmidazolium