Topic
Carcinogenesis
About: Carcinogenesis is a research topic. Over the lifetime, 60368 publications have been published within this topic receiving 3192599 citations. The topic is also known as: oncogenesis & tumorigenesis.
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TL;DR: The data indicate that LSD1 may provide a predictive marker for aggressive biology and a novel attractive therapeutic target for treatment of ER-negative breast cancers.
Abstract: Breast carcinogenesis is a multistep process involving both genetic and epigenetic changes. Since epigenetic changes like histone modifications are potentially reversible processes, much effort has been directed toward understanding this mechanism with the goal of finding novel therapies as well as more refined diagnostic and prognostic tools in breast cancer. Lysine-specific demethylase 1 (LSD1) plays a key role in the regulation of gene expression by removing the methyl groups from methylated lysine 4 of histone H3 and lysine 9 of histone H3. LSD1 is essential for mammalian development and involved in many biological processes. Considering recent evidence that LSD1 is involved in carcinogenesis, we investigated the role of LSD1 in breast cancer. Therefore, we developed an enzyme-linked immunosorbent assay to determine LSD1 protein levels in tissue specimens of breast cancer and measured very high LSD1 levels in estrogen receptor (ER)-negative tumors. Pharmacological LSD1 inhibition resulted in growth inhibition of breast cancer cells. Knockdown of LSD1 using small interfering RNA approach induced regulation of several proliferation-associated genes like p21, ERBB2 and CCNA2. Additionally, we found that LSD1 is recruited to the promoters of these genes. In summary, our data indicate that LSD1 may provide a predictive marker for aggressive biology and a novel attractive therapeutic target for treatment of ER-negative breast cancers.
453 citations
TL;DR: It is indicated that loss of both p53 alleles is not a prerequisite for tumor formation and that mere reduction in p53 levels may be sufficient to promote tumorigenesis.
Abstract: Tumor suppressor genes are generally viewed as being recessive at the cellular level, so that mutation or loss of both tumor suppressor alleles is a prerequisite for tumor formation The tumor suppressor gene, p53, is mutated in approximately 50% of human sporadic cancers and in an inherited cancer predisposition (Li-Fraumeni syndrome) We have analyzed the status of the wild-type p53 allele in tumors taken from p53-deficient heterozygous (p53+/-) mice These mice inherit a single null p53 allele and develop tumors much earlier than those mice with two functional copies of wild-type p53 We present evidence that a high proportion of the tumors from the p53+/- mice retain an intact, functional, wild-type p53 allele Unlike p53+/- tumors which lose their wild-type allele, the tumors which retain an intact p53 allele express p53 protein that induces apoptosis following gamma-irradiation, activates p21(WAF1/CIP1) and Mdm2 expression, represses PCNA expression (a negatively regulated target of wild-type p53), shows high levels of binding to oligonucleotides containing a wild-type p53 response element and prevents chromosomal instability as measured by comparative genomic hybridization These results indicate that loss of both p53 alleles is not a prerequisite for tumor formation and that mere reduction in p53 levels may be sufficient to promote tumorigenesis
453 citations
TL;DR: P16 is a major tumor-suppressor gene whose frequent loss occurs early in many human cancers and is believed that loss of p16 is an early and often critical event in tumor progression.
452 citations
TL;DR: A tamoxifen-inducible liver cancer mouse model with a defined oncogenic driver antigen is developed to follow the activation and differentiation of naive tumor-specific CD8(+) T (TST) cells after tumor initiation and shows dysfunction early during the pre-malignant phase of tumorigenesis.
452 citations
TL;DR: The purpose of the present study was to determine the miRNA expression profile of gastric cancer.
Abstract: Background and Aim: MicroRNAs (miRNAs) play important roles in carcinogenesis. The global miRNA expression profile of gastric cancer has not been reported. The purpose of the present study was to determine the miRNA expression profile of gastric cancer.
Methods: Total RNA were first extracted from primary gastric cancer tissues and adjacent non-tumorous tissues and then small isolated RNAs (< 300 nt) were 3′-extended with a poly(A) tail. Hybridization was carried out on a μParaflo™ microfluidic chip (LC Sciences, Houston, TX, USA). After hybridization detection by fluorescence labeling using tag-specific Cy3 and Cy5 dyes, hybridization images were collected using a laser scanner and digitized using Array-Pro image analysis software (Media Cybernetics, Silver Spring, MD, USA). To validate the results and investigate the biological meaning of differential expressed miRNAs, immunohistochemistry was used to detect the differential expression of target genes.
Results: The most highly expressed miRNAs in non-tumorous tissues were miR-768-3p, miR-139-5p, miR-378, miR-31, miR-195, miR-497 and miR-133b. Three of them, miR-139-5p, miR-497 and miR-768-3p, were first found in non-tumorous tissues. The most highly expressed miRNAs in gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21, miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658. Among them, miR-340*, miR-421 and miR-658 were first found highly expressed in cancer cells. The expression of some target genes (such as Rb and PTEN) in cancer tissues was found to be decreased.
Conclusion: To our knowledge, this is the first report about these miRNAs associated with gastric cancer. This new information may suggest the potential roles of these miRNAs in the diagnosis of gastric cancer.
452 citations