The Expression and Regulation of the Cell Adhesion Molecule CD44 in Human Breast Cancer.
Annual rept. 1 Aug 95-31 Jul 96,
PITTSBURGH UNIV PA
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The cell adhesion molecule CD44 is encoded by a complex gene and undergoes extensive alternative splicing. Differential regulation of CD44 splicing has been implicated in human tumorigenesis, and differences in variant isoform expression in normal versus cancerous breast tissue suggest a role for CD44 in the progression of breast cancer. Our preliminary analysis of CD44 expression in human breast samples by RT-PCR and Southern blot hybridization revealed no significant correlation between breast tumor type and CD44 variants. The retention of CD44 intron 9 was however demonstrated in 50 of breast tumors examined, supporting the hypothesis that dysregulation of CD44 splicing accompanies tumorigenesis. Novel CD44 isoforms containing single variant exons were identified in a related study of primary and metastatic tumors of the central nervous system. Analysis of similar variant isoforms in breast tumors may offer some insight into breast cancer metastasis. Examination of CD44 splicing in the human breast cancer cell lines BT-20, MDA-MB-435s and ZR-75-1 resulted in the cloning of a novel CD44 variant isoform generated by multiple splicing events. Differential usage of splicing signals associated with CD44 variant exons v2 and v3 was demonstrated in these cell lines and should allow for further delineation of exon sequences that regulate CD44 splicing in breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research