Genetic alteration of chromosome 8 is a common feature of human mammary epithelial cell lines transformed in vitro with benzo[a]pyrene.
While some epidemiological risk factors for breast cancer have been identified, the environmental factors responsible for transformation of mammary epithelial cells are not clear. We have exposed the spontaneously immortalized human mammary epithelial cell line MCF-10A to benzo[a]pyrene and selected transformed clones based on a loss of contact inhibition and anchorage-dependent growth. Cytogenetic studies showed that each of the transformed sublines possess an isochromosome 8q aberration. The c-Myc proto-oncogene, which is positioned at 8q24, was analyzed for changes in expression. Both c-Myc mRNA and protein levels were increased in the transformed clones relative to the parental cells. The transformed clones were not able to grow as tumors in vivo when injected into nude or SCID mice. To determine whether the involvement of chromosome 8 in BP-induced mutagenesis was a reproducible event, transformed clones were selected from three additional independently treated sets of BP-exposed MCF-10A cultures and analyzed by spectral karyotyping (SKY). These transformed sublines also harbored the isochromosome 8q abnormality. Data from this model show that benzo[a]pyrene, a ubiquitous procarcinogen, can induce selectable morphologic changes in a human mammary epithelial cell line, and that these transformed cells possess chromosomal aberrations frequently found in human breast tumors.
Caruso
J A
JA
McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, The Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote-Sainte-Catherine Rd., Que., H3T 1E2, Montreal, Canada.
Reiners
J J
JJ
Emond
J
J
Shultz
T
T
Tainsky
M A
MA
Alaoui-Jamali
M
M
Batist
G
G
D000818:Animals; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D001940:Breast / Q000187:drug effects / Q000473:pathology*; D015197:Carcinogenicity Tests; D002460:Cell Line; D002461:Cell Line, Transformed / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000187:drug effects* / Q000235:genetics; D002999:Clone Cells; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D051379:Mice; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D001564:Benzo(a)pyrene