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Partial suppression of tumorigenicity in a human lung cancer cell line transfected with K rev ‐1
Author(s) -
Caamano Jorge,
Dirado Marion,
Lizasa Toshihiko,
Momiki Shigeru,
Fernandes Elma,
Ashendel Curt,
Noda Makoto,
KleinSzanto Andres J. P.
Publication year - 1992
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940060406
Subject(s) - transfection , biology , cell culture , oncogene , microbiology and biotechnology , cell , reversion , neomycin , cancer research , cell cycle , gene , phenotype , genetics , antibiotics
A human non‐small‐cell lung carcinoma cell line, Calu‐6 (from an anaplastic carcinoma), was transfected with the Ki‐ ras ‐related anti‐oncogene K rev ‐1. Several transfectant lines were obtained that showed a reduced tumorigenicity in nude mice with respect to the parental and control transfected cell lines. This decrease was approximately 50% in tumor incidence at 4 wk after subcutaneous inoculation of the transfected cells. In addition, the volume of the Calu‐6 revertant‐derived tumors was three to 10 times smaller than that of the equivalent tumors produced by inoculation of the control cell line transfected with the neomycin‐resistance gene. K rev ‐1‐transfected cells that exhibited reduced tumorigenicity expressed K rev ‐1 mRNA and had variable numbers of copies of the K rev ‐1 gene. Moreover, K rev ‐1 ‐transfected cells exhibited a more differentiated squamous epithelial morphology than the parental and control cell lines did. Moderately elevated levels of protein kinase C activity were detected in some revertant clones. Such activity correlated with the level of expression of K rev ‐1 mRNA in most cases. In summary, K rev ‐1 induced important morphological and biological changes in transfected Calu‐6 cells that we interpreted as partial reversion of the malignant phenotype. © 1992 Wiley‐Liss, Inc.