Enhanced translational efficiency of a novel transforming growth factor beta 3 mRNA in human breast cancer cells.

Abstract:

:The mRNA for transforming growth factor beta 3 (TGF-beta 3) includes a long (1.1-kb) 5' noncoding region which exerts a potent inhibitory effect on translational efficiency. We now report that many human breast cancer cell lines (T47-D, SK-BR-3, ZR-75-1, and BT-474) express two mRNA species for TGF-beta 3: the 3.5-kb transcript previously described as the only TGF-beta 3 mRNA species in cells and a novel 2.6-kb transcript which lacks approximately 870 nucleotides from the 5' noncoding region. The 5' end of the shorter transcript was sequenced, establishing it to be a 5' truncation of the full-length TGF-beta 3 transcript. Estradiol decreased mRNA levels of both TGF-beta 3 mRNA transcripts to an equivalent degree in estrogen receptor-positive cells. In contrast, the synthetic progestin gestodene altered the relative abundance of the two transcripts, preferentially diminishing the expression of the 2.6-kb transcript. The potential for enhanced mRNA translation attributable to the shorter 5' noncoding region was evaluated by transfection of cells with chimeric plasmid constructs in which the transcription unit consisted of coding sequence for chloramphenicol acetyltransferase downstream of the 5' noncoding sequence from TGF-beta 3. The translational efficiency of chloramphenicol acetyltransferase-encoding mRNA containing the shorter 5' noncoding region of the 2.6-kb TGF-beta 3 transcript was approximately seven times greater than with the full-length 5' noncoding region of TGF-beta 3. Polysome analysis of TGF-beta 3 mRNA in SK-BR-3 cells supported the hypothesis that the 2.6-kb transcript was more actively engaged in translation.

journal_name

Mol Cell Biol

authors

Arrick BA,Grendell RL,Griffin LA

doi

10.1128/mcb.14.1.619

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

619-28

issue

1

eissn

0270-7306

issn

1098-5549

journal_volume

14

pub_type

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