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Prom1 function in development, intestinal inflammation, and intestinal tumorigenesis.

Karim BO, Rhee KJ, Liu G, Yun K, Brant SR - Front Oncol (2014)

Bottom Line: Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas.Also, Prom1 knockout mice are more susceptible to intestinal tumor formation.We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University , Baltimore, MD , USA.

ABSTRACT
Prom1/CD133 has been identified in colorectal, hepatocellular, and pancreatic cancer as a cancer stem cell marker and has been used as such to predict colon cancer recurrence in humans. Its potential molecular function as well as its role as a marker of intestinal regeneration is still not fully known. We evaluated the role of Prom1 in intestinal regeneration in inflammatory bowel disease (IBD), determined the function of Prom1, and characterized the effect of a lack of Prom1 on intestinal tumor formation in animal models. Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas. Also, Prom1 knockout mice are more susceptible to intestinal tumor formation. We conclude that Prom1 likely plays a role in regulating intestinal homeostasis and that these results clearly illustrate the role of Prom1 in intestinal regeneration. We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer.

No MeSH data available.


Related in: MedlinePlus

Genotypes of offspring obtained by cross-mating of Prom1−/+ and Prom1−/+ double heterozygous mice. (A) PCR of Prom1 heterozygous, wild type, and homozygous genomic DNA to detect mutant allele. (B) Mendelian ratios, single gene (Prom1) knockout.
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Figure 3: Genotypes of offspring obtained by cross-mating of Prom1−/+ and Prom1−/+ double heterozygous mice. (A) PCR of Prom1 heterozygous, wild type, and homozygous genomic DNA to detect mutant allele. (B) Mendelian ratios, single gene (Prom1) knockout.

Mentions: To determine the role of Prom1 in intestinal crypt, we analyzed Prom1-/- mice. Null mice of both sexes were phenotypically normal, and crossing heterozygous male and female mice resulted in Wt, Het, and offspring at the expected Mendelian ratios (Figure 3). Body weight analysis revealed mature obesity in Prom1-/- mice compared to Wt mice (Figure 4A). Complete histopathological analysis revealed that there is a moderate degree of germinal arrest in the testes of Prom1-/- mice compared to wild-type mice. There was multifocal seminiferous tubule atrophy and degeneration and arrest of spermatogenesis within the testes in the Prom1-/- mice at 4 months of age (Figure 4C). Serum chemistry revealed a significant increase in fasting blood glucose level in Prom1-/- mice. The mean blood glucose level was 254 mg/dl in the Prom1-/- mice compared to 158 mg/dl in the wild-type mice (Figure 4B). The knockout did not affect hematology. There were no changes in blood scores in the Prom1-/- mice compared to wild-type mice (data not shown).


Prom1 function in development, intestinal inflammation, and intestinal tumorigenesis.

Karim BO, Rhee KJ, Liu G, Yun K, Brant SR - Front Oncol (2014)

Genotypes of offspring obtained by cross-mating of Prom1−/+ and Prom1−/+ double heterozygous mice. (A) PCR of Prom1 heterozygous, wild type, and homozygous genomic DNA to detect mutant allele. (B) Mendelian ratios, single gene (Prom1) knockout.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231842&req=5

Figure 3: Genotypes of offspring obtained by cross-mating of Prom1−/+ and Prom1−/+ double heterozygous mice. (A) PCR of Prom1 heterozygous, wild type, and homozygous genomic DNA to detect mutant allele. (B) Mendelian ratios, single gene (Prom1) knockout.
Mentions: To determine the role of Prom1 in intestinal crypt, we analyzed Prom1-/- mice. Null mice of both sexes were phenotypically normal, and crossing heterozygous male and female mice resulted in Wt, Het, and offspring at the expected Mendelian ratios (Figure 3). Body weight analysis revealed mature obesity in Prom1-/- mice compared to Wt mice (Figure 4A). Complete histopathological analysis revealed that there is a moderate degree of germinal arrest in the testes of Prom1-/- mice compared to wild-type mice. There was multifocal seminiferous tubule atrophy and degeneration and arrest of spermatogenesis within the testes in the Prom1-/- mice at 4 months of age (Figure 4C). Serum chemistry revealed a significant increase in fasting blood glucose level in Prom1-/- mice. The mean blood glucose level was 254 mg/dl in the Prom1-/- mice compared to 158 mg/dl in the wild-type mice (Figure 4B). The knockout did not affect hematology. There were no changes in blood scores in the Prom1-/- mice compared to wild-type mice (data not shown).

Bottom Line: Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas.Also, Prom1 knockout mice are more susceptible to intestinal tumor formation.We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Comparative Pathobiology, The Johns Hopkins University , Baltimore, MD , USA.

ABSTRACT
Prom1/CD133 has been identified in colorectal, hepatocellular, and pancreatic cancer as a cancer stem cell marker and has been used as such to predict colon cancer recurrence in humans. Its potential molecular function as well as its role as a marker of intestinal regeneration is still not fully known. We evaluated the role of Prom1 in intestinal regeneration in inflammatory bowel disease (IBD), determined the function of Prom1, and characterized the effect of a lack of Prom1 on intestinal tumor formation in animal models. Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas. Also, Prom1 knockout mice are more susceptible to intestinal tumor formation. We conclude that Prom1 likely plays a role in regulating intestinal homeostasis and that these results clearly illustrate the role of Prom1 in intestinal regeneration. We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer.

No MeSH data available.


Related in: MedlinePlus