Reference SummaryMarsh Durban V, Am J Pathol 2014 Jan;184(1):86-91

Title

Epithelial-specific loss of PTEN results in colorectal juvenile polyp formation and invasive cancer.

Authors

Marsh Durban V; Jansen M; Davies EJ; Morsink FH; Offerhaus GJ; Clarke AR

Journal

Am J Pathol

Volume

184

Issue

1

Year

2014

Pages

86-91

Abstract

Cowden syndrome (CS) is a rare autosomal dominant cancer-prone disorder caused by germ-line mutation of the phosphatase and tensin homolog mutated on chromosome 10 (PTEN) tumor-suppressor gene. Affected patients commonly develop juvenile polyps, and show an elevated risk of developing colorectal cancers. The etiology of these peculiar polyps remains unclear, although previous work has suggested somatic PTEN alterations in the stroma of juvenile polyps. After a long latency period, we find epithelial-specific PTEN deletion to cause formation of juvenile polyps in the colorectum without stromal PTEN loss. More important, we find that these lesions closely recapitulate all of the characteristic histopathological features of juvenile polyps seen in patients with CS, including stromal alterations and dysplastic transformation to colorectal carcinoma. The stromal alterations we identify after epithelial-specific PTEN loss suggest that PTEN may be involved in altered epithelial-mesenchymal cross talk, which, in turn, predisposes to colorectal neoplasia and polyposis. Our transgenic model is the first to recapitulate colorectal juvenile polyposis in patients with CS. We conclude that stromal PTEN loss is not a prerequisite for the formation of juvenile polyps, and that colorectal juvenile polyps in CS are bona fide neoplastic precursor lesions.

Links

J:206175 – Mouse Genome Informatics
24200851 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon dysplasia
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon lesion - epithelial
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon polyp
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine - Colon tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine - Colon

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

4.35

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine adenoma - tubular
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine adenoma - tubular
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine carcinoma - invasive
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine dysplasia
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine dysplasia
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine dysplasia - focal
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine lesion - polypoid
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

100

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine neoplasia - intraepithelial
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine polyp
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine polyp
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine polyp - adenomatous
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine polyp - hyperplastic
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine polyp - hyperplastic
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Large Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Large Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenocarcinoma
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma - tubular
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed - 4.35

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine adenoma - tubular
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine dysplasia - low grade
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

4.35

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine dysplasia - low grade
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

observed

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine - Small Intestine tumor
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine - Small Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine dysplasia - low grade
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

observed

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

56.52

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine lesion
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Intestine polyp
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

56.52

[not specified]-Tg(Cyp1a1-cre/ERT)1Dwi Intestine polyp
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Intestine

0

[not specified]-Ptentm2Mak Tg(Cyp1a1-cre/ERT)1Dwi Prostate gland neoplasia
  • tamoxifen (For inducing expression from mutant alleles)
  • beta-naphthoflavone (betaNF)
Prostate gland

observed