Malignant transformation and tumor promoter treatment increase levels of a transcript for a secreted glycoprotein.

Abstract

The major excreted protein of transformed mouse fibroblasts, a secreted, mannose 6-phosphate-containing glycoprotein, is induced in nontransformed cells by a variety of transforming agents, by phorbol esters, and by platelet-derived growth factor. We report here the molecular cloning of the cDNA encoding this protein and demonstrate that its induction is a consequence of enhanced mRNA levels for major excreted protein in both tetradecanoyl phorbol acetate-treated 3T3 cells and 3T3 cells transformed by a variety of retroviruses or retroviral oncogenes. These results indicate that tumor promoters and retroviral transformation might share a common pathway of action in cultured cells and that major excreted protein is a molecular marker for the growth response of cells to these agents.

Cell and Tissue Distribution of Lysosomal Cysteine Proteinases, Cathepsins B, H, and L, and their Biological Roles.

“…It is well known that malignant transformation of mouse cells by a variety of agents results in increased synthesis and secretion of 39 kD protein termed major excreted protein (MEP) (18,25). Recent cloning of the cDNA of the protein has shown that it is identical with the cysteine proteinase, cathepsin L (17).…”

Regulation of the transcript for a lysosomal protein: evidence for a gene program modified by platelet-derived growth factor.

“…We have recently isolated several recombinant cDNA clones containing MEP sequences and identified a single 1.8-kilobase (kb) MEP RNA transcript in NIH/3T3 cells (15). Absolute levels of MEP mRNA increased after treatment of 3T3 cells with TPA or after transformation by a number of oncogenes, including v-ras or c-ras.…”

Proteins Antigenically Related to Peptides Encoded by the Mouse Mammary Tumour Virus Long Terminal Repeat Sequence Are Associated with Intracytoplasmic A Particles

“…secreted abundantly from mouse tumour cells (Gottesman & Yuspa, 1981 ;Doherty et al, 1985), precipitated C37-I RNA-encoded polypeptides of sizes similar to those reported earlier in translation of unselected polyadenylated RNAs from transformed mouse fibroblasts. Preincubation of anti-LTR serum with free peptide II abolished its reactivity with polypeptides synthesized in vitro from MMTV RNA (not shown).…”