Accession Number : ADA309880

Title :   Pleiotrophin as a Growth Factor and Therapeutic Target in Breast Cancer.

Descriptive Note : Annual rept. 15 Sep 94-14 Sep 95,

Corporate Author : GEORGETOWN UNIV WASHINGTON DC

Personal Author(s) : Wellstein, Anton

PDF Url : ADA309880

Report Date : OCT 1995

Pagination or Media Count : 20

Abstract : We studied the effect of different hormones on pleiotrophin (PTN) expression in estrogen- independent, PTN-positive breast cancer cells. We found that retinoic acid upregulates and dexamethasone downregulates PTN mRNA. In addition we expressed the PTN cDNA in PTN- negative breast cancer cells and did not find a phenotypic change in vitro. Furthermore, we generated different single cysteine-targeting mutations in the PTN protein and found that the activity of the protein was not affected by a single change in a disulfide bridge. Finally, we assessed the effects of antisense oligonucleotides, antisense mRNA and of ribozymes on the phenotype of PTN-dependent model cell lines. We found that antisense oligonucleotides can inhibit PTN expression in PTN-dependent cells and can slow the initial growth of a PTN-positive cell line in a xenograft model. However, the selectivity of the antisense oligonucleotides was only small (3-fold). Furthermore, we found that antisense transcripts can inhibit PTN expression and slow tumor growth by approximately 50% of a PTN-dependent model cell line in the athymic nude mouse model. Finally, we generated specific, PTN-targeted ribozymes that can reduce PTN mRNA in PTN-positive cells with high efficacy. The growth phenotype of a PTN-dependent model cell line was changed by the ribozyme targeting. In conclusion, we have generated a number of initial data and a series of molecular tools for our subsequent studies.

Descriptors :   *HORMONES, *NEOPLASMS, *DEOXYRIBONUCLEIC ACIDS, *RIBONUCLEIC ACIDS, *ESTROGENS, *BREAST CANCER, MOLECULES, PROTEINS, MICE, CELLS(BIOLOGY), SULFIDES, ANTIINFLAMMATORY AGENTS, MAMMARY GLANDS, ANATOMICAL MODELS, GROWTH(PHYSIOLOGY).

Subject Categories : Biology
      Anatomy and Physiology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE