Abstract:
:Mice with conditional gene deletions have been extremely valuable in allowing investigators to study the genes of interest in a tissue-specific manner. The Cre-loxP recombination system provides a powerful tool to produce targeted rearrangements of particular genes. The keratin 5-Cre recombinase (K5Cre) transgenic mouse line has been used to generate skin specific gene deletions. We found that the K5Cre mice display a unique phenotype when bred to homozygosity. The K5Cre(+/+) mice have a wavy hair coat and curly whiskers. Histologically, the hair follicles appear disoriented. Over time, the K5Cre(+/+) mice develop patches of alopecia. These mice are also runted when compared to wild-type controls. Fostering the K5Cre(+/+) pups to wild-type mothers results in normal weight gain, suggesting a maternal defect in milk production. When the K5Cre(+/+) mammary glands were examined, we not only found a significant decrease in the number of mammary branches in the virgin females, but also a greater number of quiescent alveoli units in the lactating glands. When the K5Cre(+/+) mice were bred to v-Ha-ras (Tg . AC) transgenic mice, the resulting Tg . AC(+/-) K5Cre(+/+) offspring were utilized in a chemically induced skin carcinogenesis model. The mice were treated with 2.5 microg of 12-O-tetradecanoylphorbol-13-acetate (TPA) weekly for 10 wk. No difference was observed in the time to onset of papilloma formation, the number of papillomas and the average papilloma volume between the Tg . AC(+/-) K5Cre(+/+) mice and their corresponding controls. Surprisingly, however, the K5Cre(+/+) papillomas displayed an accelerated tendency to malignant progression; in addition, the frequency of malignant transformation of the papillomas is significantly enhanced. Although the K5Cre(+/+) mice resemble waved-1 and -2 mutants, the molecular basis for the K5Cre(+/+) phenotype is probably different. In conclusion, we discovered a unique phenotype associated with the K5Cre(+/+) transgenic line.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Chan EL,Peace BE,Toney K,Kader SA,Pathrose P,Collins MH,Waltz SEdoi
10.1002/mc.20192subject
Has Abstractpub_date
2007-01-01 00:00:00pages
49-59issue
1eissn
0899-1987issn
1098-2744journal_volume
46pub_type
杂志文章abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) are carcinogens found in cooked meats that form DNA adducts upon metabolic activation. Purified DNA from Chinese hamster ovary (CHO) cells was reacted in vitro with the active metabolites N-acetoxy-IQ or N-acetoxy-Me...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940070211
更新日期:1993-01-01 00:00:00
abstract::Betanin, also called beetroot red, has been extensively used as a food colorant. In this study, the chemopreventive activity of betanin by oral consumption was investigated in two mouse lung tumor models. Vinyl carbamate (VC) and benzo(a)pyrene (B(a)P) were used to induce lung tumors, and female A/J mice were treated ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21907
更新日期:2013-09-01 00:00:00
abstract::Human colorectal cancer (CRC) cells are resistant to the anti-proliferative effect of transforming growth factor-β (TGF-β), suggesting that disruption of TGF-β signaling plays an important role in colorectal carcinogenesis. Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-β signaling by interacting...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21852
更新日期:2013-04-01 00:00:00
abstract::It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20633
更新日期:2010-06-01 00:00:00
abstract::The endocannabinoid arachidonoyl ethanolamide (AEA) is a potent inducer of tumor cell apoptosis however its mechanism of cytotoxicity is unclear. A previous report from our laboratory showed that AEA induced cell death in a cyclooxygenase-2 (COX-2)-dependent manner and in this report our data indicate that AEA-induced...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20770
更新日期:2012-02-01 00:00:00
abstract::We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H(2)O(2) or CdCl(2). Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (approximately six folds) in soft agar as compared to their JB6P+ par...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20410
更新日期:2008-07-01 00:00:00
abstract::We previously found that the small GTPase Rheb regulates the cell-cycle inhibitor p27KIP1 (p27) in colon cancer cells by a mTORC1-independent mechanism. However, the biological function of the Rheb/p27 axis in cancer cells remains unknown. Here, we show that siRNA-mediated depletion of Rheb decreases survival of human...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22272
更新日期:2016-02-01 00:00:00
abstract::Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199807)22:3<150::aid-mc2>3
更新日期:1998-07-01 00:00:00
abstract::Variations in oral bacterial communities have been linked to oral cancer suggesting that the oral microbiome is an etiological factor that can influence oral cancer development. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine oral and esophageal cancer model is frequently used to assess the effects of preventive a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22972
更新日期:2019-05-01 00:00:00
abstract::Serially transplantable rat mammary tumor (RMT) cells are not dependent on exogenous epidermal growth factor (EGF) and insulin-like growth factor-I for continuous growth in serum-free medium. Previously, we found that conditioned medium obtained from these cells contained EGF-like mitogenic activity and stimulated tyr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199602)15:2<134::AID-MC6>3
更新日期:1996-02-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. All-trans retinoic acid (ATRA) is the major physiologically active form of vitamin A, regulating expression of many genes. Disturbances of vitamin A metabolism are prevalent in some cancer cells. The main aim of this work was...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22158
更新日期:2015-09-01 00:00:00
abstract::A decrease in the intracellular concentrations of the transcripts for some tumor suppressor genes has been found during murine lung tumorigenesis; for p15INK4b and p16INK4a, this was due to homozygous deletions. We report here a decrease in the mRNA levels of the mutated in colorectal cancer (Mcc) and adenomatous poly...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Indole-3-carbinol (I3C), an anti-cancer phytochemical derived from cruciferous vegetables, strongly inhibited proliferation and down-regulated protein levels of the melanocyte master regulator micropthalmia-associated transcription factor (MITF-M) in oncogenic BRAF-V600E expressing melanoma cells in culture as well as...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22472
更新日期:2017-01-01 00:00:00
abstract::Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microar...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22670
更新日期:2017-09-01 00:00:00
abstract::We previously found that the T24 Ha-ras oncogene induces metastatic ability in NIH 3T3 cells and that this change depends on expression of the ras oncogene. As part of our studies on mechanisms by which ras may induce metastasis, we investigated expression and activity of two cysteine proteinases, cathepsin L (major e...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050311
更新日期:1992-01-01 00:00:00
abstract::Non-alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH-related liver carcinogenesis are not well understood. In the present study, we investigated cancer-associated chr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22818
更新日期:2018-08-01 00:00:00
abstract::A model of neoplastic transformation by the combination of SV40 large T antigen (LT), SV40 small T antigen (ST), oncogenic Ras, and human telomerase reverse trasncriptase subunit (hTERT) has become established and replicated in primary human fibroblasts, however, there is no report on human hepatocytes. Here we use ce...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20137
更新日期:2006-04-01 00:00:00
abstract::In epithelial ovarian cancer, tumor grade is an independent prognosticator whose molecular determinants remain unknown. We investigated patterns of gene expression in well- and poorly differentiated serous papillary ovarian and peritoneal carcinomas with cDNA microarrays. A 6500-feature cDNA microarray was used for co...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10098
更新日期:2003-02-01 00:00:00
abstract::Peptidylarginine deiminase type 4 (PAD4/PADI4) posttranslationally converts peptidylarginine to citrulline, in a process known as citrullination. Evidence suggests that PAD4 plays an essential role in pathogenesis of rheumatoid arthritis (RA). RA synovium has many features in common with tumor tissues, including abnor...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20169
更新日期:2006-03-01 00:00:00
abstract::Cell senescence and programmed cell death (apoptosis) are two fundamental biological mechanisms that regulate proliferative capacity, survival potential, aging, and death of cells. Here we report several independent lines of experimental evidence that support the hypothesis that telomerase function and telomere length...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::Microsatellite instability (MI) and loss of heterozygosity (LOH) were examined in mammary tumors induced in Sprague-Dawley x F344 F1 female rats by 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Examination of 62 microsatellite loci revealed MI in nine of 15 (60%) PhIP-induced mammary tumors, and five of thes...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199603)15:3<176::AID-MC3>3
更新日期:1996-03-01 00:00:00
abstract::Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we reported that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) [Oncogene, 2010, 29: 5241-5253]. In general, various studies established inhibition of cell proliferation by SPRY in cancer. The mechanisms by which SPRY regulates c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22379
更新日期:2016-09-01 00:00:00
abstract::Experimentally induced models of breast carcinogenesis in the rat are widely used for studying the biology of breast cancer and for developing and evaluating cancer prevention and control strategies. However, very little is known about gene expression changes that are associated with experimentally induced mammary car...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199710)20:2<204::aid-mc7>3
更新日期:1997-10-01 00:00:00
abstract::Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20590
更新日期:2010-02-01 00:00:00
abstract::Survival of patients with advanced solid tumors has not significantly improved over the past 30 years. Although molecularly targeted anticancer drugs offer promise, few drugs make it through the end of the Food and Drug Administration approval process. Animal models that more closely resemble human carcinogenesis may ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20013
更新日期:2004-04-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connec...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20793
更新日期:2012-03-01 00:00:00
abstract::Transforming growth factor beta (TGFbeta) signaling has both tumor suppression and promotion roles. Smads are transcription factors that primarily mediate intracellular signaling for the TGFbeta superfamily. Loss of Smad2 and Smad4, but not Smad3 is common in human cancers. Given the complex nature of TGFbeta signalin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20336
更新日期:2007-08-01 00:00:00
abstract::Osteosarcoma is the primary human malignant tumor affecting bone. This cancer most frequently arises in children and adolescents, with a second peak in those over the age of 50. Currently, surgery followed by radiotherapy and chemotherapy are the main treatments, but long-term positive effects are very poor. Aurora B ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22993
更新日期:2019-06-01 00:00:00
abstract::The pi-class glutathione S-transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (R...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21939
更新日期:2014-01-01 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits the proliferation of many epithelial cells through interaction with its receptors, the type I and type II receptors (TGF-beta RI and RII) by activating their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta is thoug...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199805)22:1<46::aid-mc6>3.
更新日期:1998-05-01 00:00:00