Deficiency of Splicing Factor 1 (SF1) Reduces Intestinal Polyp Incidence in Apc⁺ Mice

Area of Science:

• Molecular biology
• Genetics
• Cancer research

Background:

• Splicing factor 1 (SF1) is a key regulator of alternative splicing, present in various mammalian cell types.
• Reduced SF1 levels were studied in genetically modified mice (Sf1+/-).
• Adenomatous polyposis coli (APC) gene mutations disrupt Wnt signaling and are common in colon cancers, leading to intestinal polyps in mice (Apc).

Purpose of the Study:

• To investigate the impact of reduced SF1 levels on intestinal polyp development driven by Apc mutations.

Main Methods:

• Crossed Apc mice with Sf1+/- mice to create ApcMin/+;Sf1+/- mice.
• Compared intestinal polyp development (number, size, gender differences) between ApcMin/+;Sf1+/- and control Apc mice.

Main Results:

• Apc mice with reduced SF1 developed 25-30% fewer intestinal polyps than controls.
• This reduction was most pronounced in females.
• Fewer small polyps (≤2 mm) were observed in mice with reduced SF1, while larger polyp numbers were similar.

Conclusions:

• Reduced SF1 levels appear to inhibit the initiation of polyp development in Apc-driven intestinal tumorigenesis.
• Therapeutically lowering SF1 in the intestine could potentially reduce polyp formation.