Aujourd’hui, la sante est devenue une preoccupation sociale majeure, et la complexite des enjeux de sante ne contribue pas au besoin de securite et de certitude qui est devenu une revendication commune. Les scientifiques et les soignants, avec leurs savoirs et leurs prouesses techniques, transforment la societe qui, en retour, leur demande des pistes pour elaborer son futur. C’est dans ce contexte que « le » cancer prend une place croissante dans notre societe, et nous gagnerions a acquerir la capacite de concilier la peur qu’il nous inspire et son aptitude a nous ostraciser avec les progres que nous avons faits pour guerir ou au moins stabiliser certains cancers, qui ont transforme une maladie mortelle en une maladie chronique. L’evolution, irresistible en apparence, de la medecine vers toujours plus de technique et de precision, ne l’eloigne-t-elle pas, paradoxalement, de sa vocation d’etre au service de la personne au-dela meme de sa genetique et sa physiologie ? Nous soumettant a une certaine dictature des « sachants », ne la conduit-elle pas a definir des normes de sante auxquelles il devient difficile de se soustraire ? C’est l’ethique qui ouvre le questionnement a tous, engageant la societe dans une reflexion qui aurait pour fonction d’interpeller les modes de pensee et d’agir, de remettre en question les certitudes, les pouvoirs, les pensees dominantes et les modes.

Quelles modifications apporter a notre culture pour pouvoir evaluer des biotechnologies du type OGM

Menin, the protein encoded by the Multiple Endocrine Neoplasia type 1 gene, is involved in the cell cycle control through its participation in functional dynamics of chromatin and regulation of transcription. RB, the protein of the retinoblastoma gene RB1, controls the progression of the cell cycle and is regulated in its activity by means of a feedback by phosphorylation. Studies in double heterozygous knockout mice for Men1 and the Retinoblastoma gene Rb1 have recently indicated that both genes may be implicated in the same pathways. In the course of our studies on Menin, we found that after suppression or in absence of Menin, RB1 expression was strongly reduced in a posttranscriptional manner. Under conditions of growth arrest, the hyperphosphorylated form of RB was most strongly affected, whereas its hypophosphorylated form was less or not at all reduced. Our findings confirm the hypothesis that the pathways of two tumor suppressor genes are connected.

BACKGROUND: Mutations of the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that Men1 disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the Men1 mutant mice.METHODS: To study the occurrence of prostate lesions, we followed a male mouse cohort of 47 Men1+/- mice and 23 age-matched control littermates, starting at 18 months of age, and analysed the prostate glands from the cohort.RESULTS: Six Men1+/- mice (12.8%) developed prostate cancer, including two adenocarcinomas and four in situ carcinomas, while none of the control mice developed cancerous lesions. The expression of menin encoded by the Men1 gene was found to be drastically reduced in all carcinomas, and partial LOH of the wild-type Men1 allele was detected in three of the five analysed lesions. Using immunostaining for the androgen receptor and p63, a basal epithelial cell marker, we demonstrated that the menin-negative prostate cancer cells did not display p63 expression and that the androgen receptor was expressed but more heterogeneous in these lesions. Furthermore, our data showed that the expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a Men1 target gene known to be inactivated during prostate cell tumorigenesis, was notably decreased in the prostate cancers that developed in the mutant mice.CONCLUSION: Our work suggests the possible involvement of Men1 inactivation in the tumorigenesis of the prostate gland. PMID: 20663219

Read the full review for this Faculty Opinions recommended article: Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers.

Multiple Endocrine Neoplasia Type 1 corresponds to a monogenic predisposition syndrome inherited as a dominant trait that affects a variety of endocrine tissues, in particular parathyroids, endocrine pancreas and anterior pituitary. It is caused by mutations in the MEN1 tumor suppressor gene that inactivate menin, the MEN1 encoded protein. Menin is involved in cell cycle control and apoptosis through its participation in functional dynamics of chromatin and regulation of transcription. In addition, genetic investigations have implicated menin in the maintenance of genomic integrity. However, the role of menin does not--by far--end here. It plays (too) many roles in the control of cell life and normality, far beyond endocrine oncogenesis, making it unlikely that the function of menin can be deciphered only by genetic investigation. In this context, writing a chapter on the genetic background of MEN1 appears at the same time as a challenge and a paradox. A challenge as everything has been either already written on the topic or included in the present book. A paradox since genetics is simultaneously at the background and at the forefront of MEN1. Our attempts are thus more investigating new--as well as already open issues than delivering a catalog of MEN1 gene mutations.