The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers

The aryl hydrocarbon receptor repressor (AHRR) is a bHLH/Per-ARNT-Sim transcription factor located in a region of chromosome 5 (5p15.3) that has been proposed to contain one or more tumor suppressor genes. We report here consistent downregulation of AHRR mRNA in human malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary, and demonstrate DNA hypermethylation as the regulatory mechanism of AHRR gene silencing. Knockdown of AHRR gene expression in a human lung can- cer cell line using siRNA significantly enhanced in vitro anchorage-dependent and -independent cell growth as well as cell growth after transplantation into immunocompromised mice. In addition, knockdown of AHRR in non-clonable normal human mammary epithelial cells enabled them to grow in an anchorage-independent manner. Further, downregulation of AHRR expression in the human lung cancer cell line conferred resistance to apoptotic signals and enhanced motility and invasion in vitro and angiogenic potential in vivo. Ectopic expression of AHRR in tumor cells resulted in diminished anchorage-dependent and -independent cell growth and reduced angiogenic potential. These results therefore demonstrate that AHRR is a putative new tumor suppressor gene in multiple types of human cancers

Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer

BACKGROUND: A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. METHODS: Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method. RESULTS: Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. CONCLUSION: We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature

Toward Collaborative Print Retention

Background: :In order to serve the many member libraries who were faced with the loss of space and the subsequent need to downsize and discard print collections in a very short time, the NN/LM SE/A formed a task force on print retention in the spring of 2010. This group carried on online discussions and met twice between the Spring of 2010 and The Spring of 2011. The task force recommended, among other things, that a committee be formed to identify the potential for a collaborative print retention project in the region, develop educational resources on the topic of print retention, and recommend future directions. Methods: The ad-hoc committee met, brainstormed ideas, and developed a survey for resource and primary access libraries. The committee received responses from 128 libraries. Conclusions: An interesting and encouraging discovery was that almost one and a half times as many libraries expressed an interest in participating in a print retention project as were feeling pressure to give back space to their parent institution. This led the committee to conclude that space pressures and the resulting loss of print resources are a continuing concern for health sciences libraries. Even those who are not now facing pressures are interested in collaboration. Moreover, only a small number of the libraries were currently participating in print retention projects. The committee recommended that the NN/LM SE/A, in collaboration with the National Library of Medicine, continue work to develop a collaborative print retention project and to educate members on the resources available.https://nsuworks.nova.edu/hpd_lib_presentations/1004/thumbnail.jp

Roles for chloroplast-localized PPR Protein 30 and the “Mitochondrial” Transcription Termination Factor 9 in chloroplast quality control

Chloroplasts constantly experience photo-oxidative stress while performing photosynthesis. This is particu- larly true under abiotic stresses that lead to the accumulation of reactive oxygen species (ROS) which oxi- dize DNA, proteins and lipids. Reactive oxygen species can also act as signals to induce acclimation through chloroplast degradation, cell death and nuclear gene expression. To better understand the mechanisms behind ROS signaling from chloroplasts, we have used the Arabidopsis thaliana mutant plastid fer- rochelatase two (fc2) that conditionally accumulates the ROS singlet oxygen (1O2) leading to chloroplast degradation and eventually cell death. Here we have mapped mutations that suppress chloroplast degrada- tion in the fc2 mutant and demonstrate that they affect two independent loci (PPR30 and mTERF9) encoding chloroplast proteins predicted to be involved in post-transcriptional gene expression. These mutants exhib- ited broadly reduced chloroplast gene expression, impaired chloroplast development and reduced chloro- plast stress signaling. Levels of 1O2, however, could be uncoupled from chloroplast degradation, suggesting that PPR30 and mTERF9 are involved in ROS signaling pathways. In the wild-type background, ppr30 and mTERF9 mutants were also observed to be less susceptible to cell death induced by excess light stress. While broad inhibition of plastid transcription with rifampicin was also able to suppress cell death in fc2 mutants, specific reductions in plastid gene expression using other mutations was not always sufficient. Together these results suggest that plastid gene expression, or the expression of specific plastid genes by PPR30 and mTERF0, is a necessary prerequisite for chloroplasts to activate the 1O2 signaling pathways to induce chloroplast quality control pathways and/or cell death.12 month embargo; first published 10 August 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Roles for the chloroplast‐localized pentatricopeptide repeat protein 30 and the ‘mitochondrial’ transcription termination factor 9 in chloroplast quality control

Chloroplasts constantly experience photo-oxidative stress while performing photosynthesis. This is particu- larly true under abiotic stresses that lead to the accumulation of reactive oxygen species (ROS) which oxi- dize DNA, proteins and lipids. Reactive oxygen species can also act as signals to induce acclimation through chloroplast degradation, cell death and nuclear gene expression. To better understand the mechanisms behind ROS signaling from chloroplasts, we have used the Arabidopsis thaliana mutant plastid fer- rochelatase two (fc2) that conditionally accumulates the ROS singlet oxygen (1O2) leading to chloroplast degradation and eventually cell death. Here we have mapped mutations that suppress chloroplast degrada- tion in the fc2 mutant and demonstrate that they affect two independent loci (PPR30 and mTERF9) encoding chloroplast proteins predicted to be involved in post-transcriptional gene expression. These mutants exhib- ited broadly reduced chloroplast gene expression, impaired chloroplast development and reduced chloro- plast stress signaling. Levels of 1O2, however, could be uncoupled from chloroplast degradation, suggesting that PPR30 and mTERF9 are involved in ROS signaling pathways. In the wild-type background, ppr30 and mTERF9 mutants were also observed to be less susceptible to cell death induced by excess light stress. While broad inhibition of plastid transcription with rifampicin was also able to suppress cell death in fc2 mutants, specific reductions in plastid gene expression using other mutations was not always sufficient. Together these results suggest that plastid gene expression, or the expression of specific plastid genes by PPR30 and mTERF0, is a necessary prerequisite for chloroplasts to activate the 1O2 signaling pathways to induce chloroplast quality control pathways and/or cell death.12 month embargo; first published 10 August 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]