MT1-MMP regulates urothelial cell invasion via transcriptional regulation of Dickkopf-3

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a zinc-binding endopeptidase, which plays a crucial role in tumour growth, invasion and metastasis. We have shown previously that MT1-MMP has higher expression levels in the human urothelial cell carcinoma (UCC) tissue. We show here that siRNA against MT1-MMP blocks invasion in UCC cell lines. Invasion is also blocked by broad-spectrum protease and MMP inhibitors including tissue inhibitor of metalloproteinase-1 and -2. Membrane type-1-MMP can also regulate transcription. We have used expression arrays to identify genes that are differentially transcribed when siRNA is used to suppress MT1-MMP expression. Upon MT1-MMP knockdown, Dickkopf-3 (DKK3) expression was highly upregulated. The stability of DKK3 mRNA was unaffected under these conditions, suggesting transcriptional regulation of DKK3 by MT1-MMP. Dickkopf-3 has been previously shown to inhibit invasion. We confirm that the overexpression of DKK3 leads to decreased invasive potential as well as delayed wound healing. We show for the first time that the effects of MT1-MMP on cell invasion are mediated in part through changes in DKK3 gene transcription

The relationship between education and health among incarcerated men and women in the United States

Abstract Background This paper contributes to research on the education-health association by extending the scope of inquiry to adult inmates. Not only are inmates excluded from most nationally representative studies of health but they also represent a highly select group in terms of both education and health. As such, our study provides new information about the health of incarcerated populations and it extends the generalizability of the education-health association beyond the non-institutionalized population. Methods We use a prison-level fixed-effects regression model with the 2004 Survey of Inmates in State Correctional Facilities (n = 287 facilities) to evaluate the effects of education on a standardized morbidity scale of 11 lifetime and current health conditions among incarcerated men (n = 10,493) and women (n = 2,797). Results Education prior to incarceration is negatively associated with lifetime health problems for both women and men and the association is stronger among women. Among inmates who enter prison with less than a GED level of education, attaining a GED in prison is associated with better current health outcomes for men, but not women. Conclusions The generalization of the education-health association among prisoners further highlights the fundamental nature of education as a health promotive resource. Discussed are the implications for the education-health literature in general and health promotion efforts among incarcerated adults specifically

Recidivism in HIV-Infected Incarcerated Adults: Influence of the Lack of a High School Education

Recidivism is a pervasive problem facing the incarcerated. Incarcerated persons who are human immunodeficiency virus (HIV)-infected often have multiple risk factors associated with initial incarceration and recidivism, in particular, injection drug use. Yet, some jails provide case management for HIV-infected inmates to provide continuity of health care, which might have positive effects on reentry into the community. We sought to measure recidivism and factors related to recidivism in an HIV-infected cohort in an urban county jail with an active case management program. Fifty-two inmates surveyed in 1999 at the San Francisco County Jail were followed for rearrests through 2006. In follow-up, 73% were re-incarcerated on an average of 6.8 times for 552 days. Risk factors included nonwhite ethnicity, history of homelessness and crack use, common risk factors for incarceration. Less than high school education was associated with recidivism, shorter time to reincarceration, and more incarcerations. HIV-infected inmates spend a high proportion of time in multiple incarcerations, a reflection of the cyclical nature of incarceration despite comprehensive case management. Well-known risk factors for incarceration were associated with recidivism; in addition, lack of high school education played a prominent role. Education should be explored as a way to make further progress on breaking the cycle of incarceration

From syndrome families to functional genomics.

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