Disease relevance of SASH1

• SASH1 is downregulated in the majority (74%) of breast tumors in comparison with corresponding normal breast epithelial tissues [1].
• We show augmentation of motility associated with morphological changes of human squamous carcinoma SASH1 cells, human peripheral monocytes (hPMs), and murine macrophage-like cell line J774.1 by superoxide stimulation [2].
• Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer [3].
• Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases [3].
• However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I) [3].

High impact information on SASH1

• In breast cancer cell lines, SASH1 is only expressed at low levels [1].
• SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer [1].
• Systematic comparison of candidate EST sequences with genomic sequences from this interval revealed the genomic structure of a potential target gene on 6q24.3, which we called SAM and SH3 domain containing 1 (SASH1) [1].
• In addition, SASH1 is also downregulated in tumors of the lung and thyroid [1].
• Analysis of the protein domain structure revealed that SASH1 is a member of a recently described family of SH3/SAM adapter molecules and thus suggests a role in signaling pathways [1].

Biological context of SASH1

• We assume that SASH1 is a new tumor suppressor gene possibly involved in tumorigenesis of breast and other solid cancers [1].
• We therefore hypothesize that other mechanisms as for instance methylation of the promoter region of SASH1 are responsible for the loss of expression of SASH1 in primary and metastatic breast cancer [1].
• Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival [3].

Anatomical context of SASH1

• Two SASH1 transcripts of approximately 4.4 and 7.5 kb exist and are predominantly transcribed in the human breast, lung, thyroid, spleen, placenta and thymus [1].
• SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein-protein interaction domains [3].

Associations of SASH1 with chemical compounds

• Using a combination of reference tests to assess the accuracy of a diagnostic test by A. Alonzo and M. Pepe, Statistics in Medicine 1999; 18: 2987-3003 [4].

Analytical, diagnostic and therapeutic context of SASH1

• We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples [3].
• We demonstrate that PEPEP is a very efficient dye for fluorescence confocal microscopy and a valuable alternative to the most frequently used mitochondrial stains [5].

References