CLONING, STRUCTURE-FUNCTION RELATIONSHIP AND MOLECULAR MECHANISM OF THE REGULATION AND EXPRESSION OF STEROIDOGENESIS ENZYMES IN PERIPHERAL TISSUES. THE ROLE OF THESE ENZYMES IN THE ANDROGEN- AND ESTROGEN-DEPENDANT DISEASES.

Hormono-dependant cancers, namely breast and prostate cancers, are the most frequently occuring cancers. These diseases strike 1 in 9 women, and 1 in 8 men in their lifetime. Our laboratory has shown the important role played by the hormones biosynthetized in peripheral tissues, and the intracellular autonomous control of the steroid hormone levels. We have therefore cloned and identified several of the cDNAs and gene encoding enzymes of the steroidogenic pathway, namely, 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-HSDs, 3a-HSDs, 20a-HSDs, 5a-reductases, and sulfotransferases. Our research program will focus on the study of:

1) the structure-function relationships,

2) the molecular mechanisms involved in the regulation and expression of these enzymes in peripheral tissues,

3) the role of these enzymes in estrogen- and androgeno-sensitive diseases, and

4) the cloning and identification of new enzymes in the steroidogenic pathway.

The techniques currently being used are: those of molecular biology, cloning, construction of expression vectors, site directed mutagenesis, transfection in mammalian cells, overexpression using baculovirus and bacteria, enzyme kinetic and molecular modelization.

These projects are supported by the Medical Research Council Group in Molecular Endocrinology.

 

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Luu-The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F (1989) Full length cDNA structure and deduced amino acid sequence of human 3ß-hydroxy-5-ene steroid dehydrogenase. Mol Endocrinol 3: 1310-1312.

Luu-The V, Lachance Y, Simard J, Labrie C, Zhao HF, Couet J, Leblanc G, Labrie F (1990) Structure of two in tandem human 17ß-hydroxysteroid dehydrogenase genes. Mol Endocrinol 4: 268-275.

Bernier F, Leblanc G, Labrie F, Luu-The V (1994) Structure of human estrogen and aryl sulfotransferase gene: two mRNA species issued from a single gene. J Biol Chem 269: 28200-28205.

Guerin SL, Leclerc S, Verreault H, Labrie F, Luu-The V (1995) Overlapping cis-acting elements located in the first intron of the gene for type I 3ß-hydroxysteroid dehydrogenase modulate its transcriptional activity. Mol Endocrinol 9: 1583-1597.

Luu-The V, Dufort I, Paquet N, Reimnitz G, Labrie F (1995) Structural characterization and expression of the human dehydroepiandrosterone sulfotransferase gene. DNA Cell Biol 14: 511-518.