The Mom1(AKR) intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64

Robert T. Cormier, Andrea Bilger, Amy J. Lillich, Richard B. Halberg, Karen H. Hong, Karen A Gould, Natalie Borenstein, Eric S. Lander, William F. Dove

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during a screen for polymorphic modifiers of intestinal tumorigenesis in Apc(Min/+) mice. Here, we demonstrate that the Mom1(AKR) allele consists of two genetic components. These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines. A second region, distal to Pla2g2a, has also been identified using fine structure recombinants. Pla2g2a(AKR) transgenic mice demonstrate a modest resistance to tumorigenesis in the small intestine and a very robust resistance in the large intestine. Moreover, the tumor resistance in the colon of Pla2g2a(AKR) animals is dosage-dependent, a finding that is consistent with our observation that Pla2g2a is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier demonstrate a modest tumor resistance that is confined to the small intestine. Thus, the phenotypes of these two modifier loci are complementary, both in their quantitative and regional effects. The additive effects and tight linkage of these modifiers may have been necessary for the initial identification of the Mom1 region.

Original languageEnglish (US)
Pages (from-to)3182-3192
Number of pages11
JournalOncogene
Volume19
Issue number28
DOIs
StatePublished - Jun 29 2000

Fingerprint

Small Intestine
Carcinogenesis
Inbred AKR Mouse
Chromosomes, Human, Pair 4
Goblet Cells
Phospholipases
Large Intestine
Transgenic Mice
Neoplasms
Colon
Alleles
Phenotype

Keywords

  • Apc
  • Goblet cell
  • Min mouse
  • Mom1
  • Pla2g2a
  • Tumor resistance

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Cormier, R. T., Bilger, A., Lillich, A. J., Halberg, R. B., Hong, K. H., Gould, K. A., ... Dove, W. F. (2000). The Mom1(AKR) intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. Oncogene, 19(28), 3182-3192. https://doi.org/10.1038/sj.onc.1203646

The Mom1(AKR) intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. / Cormier, Robert T.; Bilger, Andrea; Lillich, Amy J.; Halberg, Richard B.; Hong, Karen H.; Gould, Karen A; Borenstein, Natalie; Lander, Eric S.; Dove, William F.

In: Oncogene, Vol. 19, No. 28, 29.06.2000, p. 3182-3192.

Research output: Contribution to journalArticle

Cormier, RT, Bilger, A, Lillich, AJ, Halberg, RB, Hong, KH, Gould, KA, Borenstein, N, Lander, ES & Dove, WF 2000, 'The Mom1(AKR) intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64', Oncogene, vol. 19, no. 28, pp. 3182-3192. https://doi.org/10.1038/sj.onc.1203646
Cormier, Robert T. ; Bilger, Andrea ; Lillich, Amy J. ; Halberg, Richard B. ; Hong, Karen H. ; Gould, Karen A ; Borenstein, Natalie ; Lander, Eric S. ; Dove, William F. / The Mom1(AKR) intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64. In: Oncogene. 2000 ; Vol. 19, No. 28. pp. 3182-3192.
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