Reduction of Cripto-1 expression by a hammerhead-shaped RNA molecule results from inhibition of translation rather than mRNA cleavage.

Abstract:

:Cripto-1 (CR-1) is a transforming growth factor which has been associated with breast, colon, and pancreatic cancer. Overexpression of CR-1 in non-tumorigenic mouse mammary epithelial cells and fibroblasts results in an increase in anchorage-dependent and -independent growth in vitro. Reduction of CR-1 expression in human colon carcinoma or embryonal teratoma cells results in a decrease in growth in vitro. In an effort to better define the role of CR-1 in breast cancer, we have developed an underexpression vector for CR-1 to reduce CR-1 levels in a tumorigenic mouse mammary epithelial cell line (-SA). This vector specifically targets the expression of the murine homolog of CR-1 in murine cancer lines and utilizes a hammerhead ribozyme-like structure directed toward the extreme 5' end of the Cripto-1 mRNA. We dramatically reduced expression of CR-1 through the expression of this RNA. This is the first use of a ribozyme-like molecule to alter Cripto-1 expression. This ribozyme-shaped molecule appears to act principally through a block in translation. A possible mechanism for this block is described, and its implications for modifying expression of other bioactive proteins are discussed.

authors

Kintner RL,Hosick HL

doi

10.1006/bbrc.1998.8517

subject

Has Abstract

pub_date

1998-04-28 00:00:00

pages

774-9

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98517-5

journal_volume

245

pub_type

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