10 research outputs found
Human cancers over express genes that are specific to a variety of normal human tissues
We have analyzed gene expression data from 3 different kinds of samples:
normal human tissues, human cancer cell lines and leukemic cells from lymphoid
and myeloid leukemia pediatric patients. We have searched for genes that are
over expressed in human cancer and also show specific patterns of
tissue-dependent expression in normal tissues. Using the expression data of the
normal tissues we identified 4346 genes with a high variability of expression,
and clustered these genes according to their relative expression level. Of 91
stable clusters obtained, 24 clusters included genes preferentially expressed
either only in hematopoietic tissues or in hematopoietic and 1-2 other tissues;
28 clusters included genes preferentially expressed in various
non-hematopoietic tissues such as neuronal, testis, liver, kidney, muscle,
lung, pancreas and placenta. Analysis of the expression levels of these 2
groups of genes in the human cancer cell lines and leukemias, identified genes
that were highly expressed in cancer cells but not in their normal
counterparts, and were thus over expressed in the cancers. The different cancer
cell lines and leukemias varied in the number and identity of these over
expressed genes. The results indicate that many genes that are over expressed
in human cancer cells are specific to a variety of normal tissues, including
normal tissues other than those from which the cancer originated. It is
suggested that this general property of cancer cells plays a major role in
determining the behavior of the cancers, including their metastatic potential.Comment: To appear in PNA
Induction in myeloid leukemic cells of genes that are expressed in different normal tissues
Using DNA microarray and cluster analysis of expressed genes in a cloned line
(M1-t-p53) of myeloid leukemic cells, we have analyzed the expression of genes
that are preferentially expressed in different normal tissues. Clustering of
547 highly expressed genes in these leukemic cells showed 38 genes
preferentially expressed in normal hematopoietic tissues and 122 other genes
preferentially expressed in different normal non-hematopoietic tissues
including neuronal tissues, muscle, liver and testis. We have also analyzed the
genes whose expression in the leukemic cells changed after activation of
wild-type p53 and treatment with the cytokine interleukin 6 (IL-6) or the
calcium mobilizer thapsigargin (TG). Out of 620 such genes in the leukemic
cells that were differentially expressed in normal tissues, clustering showed
80 genes that were preferentially expressed in hematopoietic tissues and 132
genes in different normal non-hematopietic tissues that also included neuronal
tissues, muscle, liver and testis. Activation of p53 and treatment with IL-6 or
TG induced different changes in the genes preferentially expressed in these
normal tissues. These myeloid leukemic cells thus express genes that are
expressed in normal non-hematopoietic tissues, and various treatments can
reprogram these cells to induce other such non-hematopoietic genes. The results
indicate that these leukemic cells share with normal hematopoietic stem cells
the plasticity of differentiation to different cell types. It is suggested that
this reprogramming to induce in malignant cells genes that are expressed in
different normal tissues may be of clinical value in therapy
The prevalence of upper extremity musculoskeletal disorders among dental hygienist and students of dental hygiene
Transcription factor/microRNA axis blocks melanoma invasion program by miR-211 targeting NUAK1
Melanoma is one of the deadliest human cancers, responsible for approximately 80% of skin cancer mortalities. The aggressiveness of melanoma is due to its capacity to proliferate and rapidly invade surrounding tissues, leading to metastases. A recent model suggests melanoma progresses by reversibly switching between proliferation and invasion transcriptional signatures. Recent studies show that cancer cells are more sensitive to microRNA (miRNA) perturbation than are non-cancer cells; however, the roles of miRNAs in melanoma plasticity remain unexplored. Here, we use the gene expression profiles of melanoma and normal melanocytes to characterize the transcription factor-miRNA relationship that modulates the proliferative and invasive programs of melanoma. We identified two sets of miRNAs that likely regulate these programs. Interestingly, one of the miRNAs involved in melanoma invasion is miR-211, a known target of the master regulator microphthalmia-associated transcription factor (MITF). We demonstrate that miR-211 contributes to melanoma adhesion by directly targeting a gene, NUAK1. Inhibition of miR-211 increases NUAK1 expression and decreases melanoma adhesion, whereas upregulation of miR-211 restores adhesion through NUAK1 repression. This study defines the MITF/miR-211 axis that inhibits the invasive program by blocking adhesion. Furthermore, we have identified NUAK1 as a potential target for the treatment of metastatic melanoma. 2014 The Society for Investigative Dermatolog