Deletion and differential expression of p16{sup INK4a} in mouse lung tumors

Journal Article · Wed Dec 31 04:00:00 EST 1997 · Carcinogenesis

DOI:https://doi.org/10.1093/carcin/18.1.115· OSTI ID:613727

Belinsky, S A; Swafford, D S; Middleton, S K; Kennedy, C H; Tesfaigzi, J ^[1]

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1. Inhalation Toxicology Research Institute, Albuquerque, NM (United States)

Recent allelotyping of chemical-induced lung tumors in hybrid mice has detected loss of heterozygosity on chromosome 4 in a region involving the interferon-{alpha} (IFN-{alpha}) gene cluster that is syntenic to human chromosome 9p21-22, the location of the p16{sup INK4a}(p16) and (p15) tumor suppressor genes. The purpose of the current investigation was to characterize the expression of p16 and p15 in lung tumors and tumor-derived cell lines induced in Ad mice by exposure to the tobacco-specific nitrosamine, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK). Expression of p16 and p15 was detected in all primary lung tumors; however, levels of expression of p16 differed by up to 15-fold between tumors. This is the first study to note a marked difference in the expression of the p16 gene in primary lung tumors. The apparent low levels of expression seen in approximately half of the tumors was not attributed to deletion, mutation or methylation of the p16 gene. Conversely, the high levels of p16 expression were not the result of effects on the retinoblastoma gene (Rb) or cyclin D1 proteins but most likely in response to a dysfunction elsewhere within this pathway. In contrast to the detection of p16 expression in primary tumors, this gene was deleted in all four cell lines. Three of four cell lines also showed loss of the p15 gene. Mapping of these homozygous deletions on chromosome 4 revealed that the p16 gene resides near the D4MIT77 marker, which is located approximately 12 cM proximal to the IFN-{alpha} gene cluster, thereby implicating the p16 gene as one of the targets within the allelic deletions detected previously in primary lung tumors from hybrid mice.

• OSTI ID: 613727
• Journal Information: Carcinogenesis, Journal Name: Carcinogenesis Journal Issue: 1 Vol. 18; ISSN CRNGDP; ISSN 0143-3334
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
AMINES
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
GENES
GENETIC EFFECTS
GENETIC MAPPING
LUNGS
MICE
NEOPLASMS
TOBACCO