Loss of expression of human spectrin src homology domain binding protein 1is associated with 10p loss in human prostatic adenocarcinoma

The gene encoding human spectrin Src homology domain binding protein I, or Hssh3bp1, which is a marker of macropinocytic vesicles and a potential regu lator of macropinocytosis, co-localizes to a YAC containing chromosome 10p sequences at loci D10S89 and D10S111 that are frequently deleted in prostat e tumors. Expression of Hssh3bp1 was evaluated at the protein level in II p aired normal and malignant prostate tumor samples using the monoclonal anti body 2G8 to Hssh3bp1. These experiments demonstrated that 4/6 tumors (67%) with 10p deletion failed to express Hssh3bp1 protein compared to 5/11 (46%) tumors with intact 10p. Thus, loss of Hssh3bp1 expression is concordant wi th allelic loss of adjacent 10p sequences in human prostate tumors, In addi tion, two prostate tumor cell lines contain an exon skipping mutation in th e Hssh3bp1 gene that leads to the abnormal splicing of the mRNA and loss of a portion of Abl tyrosine kinase SH3 domain binding site in the protein. T hese data are consistent with a role for Hssh3bp1 as a candidate tumor supp ressor gene inactivated during prostate tumorigenesis.