A putative role for oncogenes in trophoblast invasion?
Tumour invasion and trophoblastic invasion share the same biochemical mediators: the matrix metalloproteinases (MMP) and their inhibitors (TIMP). MMP are a family of enzymes capable of digesting the extracellular matrices of the host tissues. Human cytotrophoblastic cells are constitutively invasive and produce MMP. That MMP are causally related to trophoblast invasion in the endometrium is shown by the fact that TIMPs inhibit cytotrophoblastic invasion in vitro. In contrast to tumour invasion of a host tissue, trophoblastic invasion during implantation and placentation is stringently controlled both in space and time. The factors responsible for these important regulatory processes are unknown, but in-vitro studies point to autocrine (trophoblastic) and paracrine (endometrial) controls by cytokines and growth factors. These regulators exert their effects directly or indirectly by activating nuclear transcription factors. Transcription factors are proteins or protein complexes (often the products of oncogenes) that activate genes by binding to specific sites of the DNA located in the regulatory (5' flanking) region of genes. This review describes the different DNA binding domains of the MMP-9 gene, summarizes our knowledge about the transcription factors involved and speculates about a potential role of these transcription factors (particularly the oncogenes Jun and Fos) in regulating trophoblast invasion.
Bischof
P
P
Department of Obstetrics and Gynaecology, University of Geneva, Switzerland. paul.bischof@hcuge.ch
Campana
A
A
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009857:Oncogenes; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000502:physiology*
D014157:Transcription Factors; D004247:DNA; D020780:Matrix Metalloproteinase 9