Oncogene expression in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene.
Expression of four oncogenes and two keratin genes was determined in rat tracheal epithelial cell lines derived from tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. Cell lines were grouped into four stages of neoplastic progression based on phenotypic markers in order to correlate oncogene expression with stage of malignancy. Northern analysis of RNA revealed a significantly enhanced expression of the c-myc oncogene in the most tumorigenic or tumor-derived cell lines, whereas preneoplastic cells expressed approximately five-fold less transcript. Southern analysis of tracheal cell DNA did not demonstrate amplification of the c-myc gene in any of the positive cell lines. In contrast to c-myc, other oncogenes such as ras and fos were expressed in all cell lines, as well as in control cell cultures, to a similar extent. Patterns of differentiation were examined in these epithelial cell lines by determining the expression of two distinct keratin genes, KA-1 and KB-2. Both malignant and preneoplastic cells expressed the KB-2 gene at variably high levels, whereas the expression of the KA-1 keratin was barely detectable in any of the cell lines. The stage-specific expression of the c-myc oncogene in these tracheal cell lines suggests a correlation between the regulation of certain oncogenes and neoplastic progression in this model of respiratory carcinogenesis.
Cosma
G N
GN
Department of Environmental Medicine, New York University Medical Center, NY 10016.
Marchok
A C
AC
Garte
S J
SJ
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D007633:Keratins / Q000235:genetics*; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014134:Tracheal Neoplasms / Q000235:genetics* / Q000473:pathology
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins; D015689:Oncogene Protein p21(ras)