Loss of Expression of Human Spectrin Src Homology Domain Binding Protein 1 is Associated with 10p Loss in Human Prostatic Adenocarcinoma

Abstract

The gene encoding human spectrin Src homology domain binding protein 1, or Hssh3bp1, which is a marker of macropinocytic vesicles and a potential regulator of macropinocytosis, co-localizes to a YAC containing chromosome 10p sequences at loci D10S89 and D10S111 that are frequently deleted in prostate tumors. Expression of Hssh3bp1 was evaluated at the protein level in 17 paired normal and malignant prostate tumor samples using the monoclonal antibody 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 with allelic loss of adjacent 10p sequences in human prostate tumors. In addition, two prostate tumor cell lines contain an exon skipping mutation in the 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. These data are consistent with a role for Hssh3bp1 as a candidate tumor suppressor gene inactivated during prostate tumorigenesis.

Abelson Interactor Protein-1 Positively Regulates Breast Cancer Cell Proliferation, Migration, and Invasion

“…Some reports have indicated that overexpression of ABI-1 inhibits growth and transforming activity of v-Abl in NIH3T3 cells as well as epidermal growth factorinduced and v-Abl -induced activation of extracellular signalregulated kinase in 293T cells (12,(19)(20)(21)(22), which suggest a potential negative regulatory role of ABI-1 on epidermal growth factor -mediated signaling. Other studies have found that loss of ABI-1 may play a role in human prostatic adenocarcinoma and the oncogenesis of Bcr-Abl -positive leukemia (23,24). However, experiments with Drosophila suggest that both fly and human ABI-1 can enhance the ability of Abl to Columns, mean of three independent experiments in siRNA clones 2, 9, and 11; bars, SE.…”

A gene signature identified using a mouse model of androgen receptor‐dependent prostate cancer predicts biochemical relapse in human disease

“…Notable genes elevated in the AR-E231G model included Rb1 32 and Ccr2, 33 both of which have been shown to be overexpressed in clinical prostate cancer, and Pmaip1, a gene that is predictive of BCR in human disease. 34 Expression of the tumor suppressor genes Vangl2, Apc and Abi1 35,36 was reduced in AR-E231G samples. Ten of the 13 members of the androgen-responsive and mouse-specific kallikrein Klk1b family were increased in AR-E231G prostates, suggesting that these factors could be a useful marker of prostate cancer initiation in mouse models.…”

The Role of Human Spectrin SH3 Domain Binding Protein 1 (HSSH3BP1) in Prostatic Adenocarcinoma

“…We hypothesized that tumorigenicity of some prostate cell lines is due to inactivation of Hssh3bpl function. We determined that LnCaP cell lines, ATCC CRL-10995 and -1740 contain an exon-skipping HsshSbpl mutation (Macoska et al, 2001). Thus it is possible that HsshSbpl function is impared in these cell lines.…”

“…Thus it is hypothesized that expression of HsshSbpl will slow growth of these cells and lower tumorigenicity in nude mice. We also plan to test whether overexpression Hssh3bpl mutation found in LnCAP cell line (Macoska et al, 2001) induces PC3 cells to grow faster. These experiments are consistent with Aim 2b.…”

“…Purified recombinant Abl kinase was purchased from New England Biolabs. In vitro translated HsshSbpl (Macoska et al, 2001) was immunopreciptated with antibody Ab-2 as described (Xu et al, 2000) in the presence of phosphatase inhibitors such as orthovanadate and P-glycerophosphate (Fig. Sa).…”