Abstract:
:Tyrosine phosphorylation-dependent signaling, as mediated by members of the epidermal growth factor receptor (EGFR) family (ErbB1 to -4) of protein tyrosine kinases (PTKs), Src family PTKs (SFKs), and cytokines such as interleukin-6 (IL-6) that signal via signal transducer and activator of transcription 3 (STAT3), is critical to the development and progression of many human breast cancers. EGFR, SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase TCPTP (PTPN2). Here we report that TCPTP protein levels are decreased in a subset of breast cancer cell lines in vitro and that TCPTP protein is absent in a large proportion of "triple-negative" primary human breast cancers. Homozygous TCPTP deficiency in murine mammary fat pads in vivo is associated with elevated SFK and STAT3 signaling, whereas TCPTP deficiency in human breast cancer cell lines enhances SFK and STAT3 signaling. On the other hand, TCPTP reconstitution in human breast cancer cell lines severely impaired cell proliferation and suppressed anchorage-independent growth in vitro and xenograft growth in vivo. These studies establish TCPTP's potential to serve as a tumor suppressor in human breast cancer.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Shields BJ,Wiede F,Gurzov EN,Wee K,Hauser C,Zhu HJ,Molloy TJ,O'Toole SA,Daly RJ,Sutherland RL,Mitchell CA,McLean CA,Tiganis Tdoi
10.1128/MCB.01016-12subject
Has Abstractpub_date
2013-02-01 00:00:00pages
557-70issue
3eissn
0270-7306issn
1098-5549pii
MCB.01016-12journal_volume
33pub_type
杂志文章abstract::The SMRT corepressor complex participates in transcriptional repression by a diverse array of vertebrate transcription factors. The ability to recruit SMRT appears to play a crucial role in leukemogenesis by the PML-retinoic acid receptor alpha (RARalpha) oncoprotein, an aberrant nuclear hormone receptor implicated in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7172-7182.2001
更新日期:2001-11-01 00:00:00
abstract::Saccharomyces mating-type switching occurs through a double-strand break-initiated gene conversion event at MAT, using one of two donors located distantly on the same chromosome, HMLalpha and HMRa. MATa cells preferentially choose HMLalpha, a decision that depends on the recombination enhancer (RE) that controls recom...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02443-05
更新日期:2006-07-01 00:00:00
abstract::Methyl-accepting assays and a sensitive method for labeling specific CpG sites have been used to show that the DNA of F9 embryonal carcinoma cells decreases in 5-methylcytosine content by ca. 9% during retinoic acid-induced differentiation, whereas the DNA of dimethyl sulfoxide-induced Friend murine erythroleukemia (M...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.9.1800
更新日期:1984-09-01 00:00:00
abstract::A molecular karyotype of Neurospora crassa was obtained by using an alternating-field gel electrophoresis system which employs contour-clamped homogeneous electric fields. The migration of all seven N. crassa chromosomal DNAs was defined, and five of the seven molecules were separated from one another. The estimated s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1469
更新日期:1988-04-01 00:00:00
abstract::Progression through mitosis requires the inactivation of the protein kinase activity of the p34cdc2-cyclin complex by a mechanism involving the degradation of cyclin. We have examined the stability in Xenopus egg extracts of radiolabeled Xenopus or sea urchin B-type cyclins synthesized in reticulocyte lysates. Xenopus...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1480
更新日期:1993-03-01 00:00:00
abstract::Moloney murine sarcoma virus carries an oncogenic sequence (v-mos) which is homologous to a single copy gene (c-mos) present in the normal cells of several vertebrate species. Because of the possible significance of c-mos sequences in normal development and malignant transformation induced by physical or chemical agen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.1.42
更新日期:1982-01-01 00:00:00
abstract::A Dictyostelium discoideum cDNA encoding an alpha-type subunit of casein kinase II was isolated, and its cDNA was used to study developmental expression of casein kinase II during the Dictyostelium life cycle. The 1.3-kb cDNA insert contained an open reading frame of 337 amino acids (M(r) 39,900). The deduced amino ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.12.5711
更新日期:1992-12-01 00:00:00
abstract::Mutations in the Saccharomyces cerevisiae alpha-factor receptor that lead to improved response to Saccharomyces kluyveri alpha-factor were identified and sequenced. Mutants were isolated from cells bearing randomly mutagenized receptor gene (STE2) plasmids by an in vivo screen. Five mutations lead to substitutions in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.9.3959
更新日期:1992-09-01 00:00:00
abstract::LFB1 (HNF1) is a tissue-specific transcription factor found in the livers, stomachs, intestines, and kidneys of vertebrates. By analyzing the promoter of the Xenopus LFB1 gene, we identified potential autoregulation by LFB1 and regulation by HNF4, a transcription factor with a tissue distribution similar to that of LF...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6416
更新日期:1993-10-01 00:00:00
abstract::We have analyzed the fine structure of DNA repair in Chinese hamster ovary (CHO) cells within the G1 and G2 phases of the cell cycle. Repair of inactive regions of the genome has been suggested to increase in the G2 phase of the cell cycle compared with other phases. However, detailed studies of DNA repair in the G2 p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.7.3731
更新日期:1995-07-01 00:00:00
abstract::Appropriate cell cycle checkpoint control is essential for the maintenance of cell and organismal homeostasis. Members of the Nek (NIMA-related kinase) family of serine/threonine protein kinases have been implicated in the regulation of various aspects of the cell cycle. We explored the cellular functions of Nek10, a ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00648-10
更新日期:2011-01-01 00:00:00
abstract::Translation is a fundamental step in gene expression, and translational control is exerted in many developmental processes. Most eukaryotic mRNAs are translated by a cap-dependent mechanism, which requires recognition of the 5'-cap structure of the mRNA by eukaryotic translation initiation factor 4E (eIF4E). eIF4E act...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01354-12
更新日期:2013-08-01 00:00:00
abstract::Minisatellite DNA is repetitive DNA with a repeat unit length from 15 to 100 bp. While stable during mitosis, it destabilizes during meiosis, altering both in length and in sequence composition. The basis for this instability is unknown. To investigate the factors controlling minisatellite stability, a minisatellite s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.3.953-964.2002
更新日期:2002-02-01 00:00:00
abstract::As part of an effort to characterize the spatial and functional relationships among genetic elements within the amplified dihydrofolate reductase (DHFR) domain in Chinese hamster cells, we have used a variation of the differential hybridization approach to identify cDNA clones whose genes are coamplified with DHFR in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.3.1137
更新日期:1989-03-01 00:00:00
abstract::The cytoplasmic domain of the cloned erythropoietin (EPO) receptor (EPOR) contains no protein kinase motif, yet addition of EPO to EPO-responsive cells causes an increase in protein-tyrosine phosphorylation. Here we show that addition of EPO or interleukin-3 (IL-3) to an IL-3-dependent cell line expressing the wild-ty...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.2.706
更新日期:1992-02-01 00:00:00
abstract::The gene encoding the 180-kDa DNA strand transfer protein beta from the yeast Saccharomyces cerevisiae was identified and sequenced. This gene, DST2 (DNA strand transferase 2), was located on chromosome VII. dst2 gene disruption mutants exhibited temperature-sensitive sporulation and a 50% longer generation time durin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.5.2583
更新日期:1991-05-01 00:00:00
abstract::Previous analyses defined a proliferating cell nuclear antigen (PCNA) E1A-responsive element (PERE) in the PCNA promoter that is essential for transactivation by the 243-residue product of the adenovirus type 2 E1A 12S mRNA (E1A 243R). In this report, we show that the PERE activates a heterologous basal promoter and c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.543
更新日期:1994-01-01 00:00:00
abstract::Genomic imprinting results in parent-of-origin-dependent monoallelic expression of selected genes. Although their importance in development and physiology is recognized, few imprinted genes have been investigated for their effects on brain function. Gnas is a complex imprinted locus whose gene products are involved in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.8.3019-3026.2005
更新日期:2005-04-01 00:00:00
abstract::In resting cells, the NFAT1 transcription factor is kept inactive in the cytoplasm by phosphorylation on multiple serine residues. These phosphorylated residues are primarily contained within two types of serine-rich motifs, the SRR-1 and SP motifs, which are conserved within the NFAT family. Several different kinases...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.10.4184-4195.2004
更新日期:2004-05-01 00:00:00
abstract::Using a hybridoma cell line which secretes hapten-specific immunoglobulin M (IgM), we have isolated a variety of mutants which produce abnormal immunoglobulin. Immunoglobulin was tested for the size and composition of the component heavy and light chains and for variable and constant region related functional and sero...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.9.1033
更新日期:1982-09-01 00:00:00
abstract::RNA polymerase III (pol III) transcripts of the highly repeated mouse B2 gene family are increased in many oncogenically transformed murine cell lines. In cells transformed by simian virus 40, the small, cytoplasmic B2 RNAs are present at 20-fold-higher levels than in normal cells (M. R. D. Scott, K. Westphal, and P. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.9.3068
更新日期:1986-09-01 00:00:00
abstract::Expression of the Saccharomyces cerevisiae CYC1 gene produces mRNA with more than 20 different 5' ends. A derivative of the CYC1 gene (CYC1-157) was constructed with a deletion of a portion of the CYC1 5'-noncoding region, which includes the sites at which many of the CYC1 mRNAs 5' ends map. A 54-mer double-stranded o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.12.3545
更新日期:1985-12-01 00:00:00
abstract::We have cloned CDC9, the structural gene for Saccharomyces cerevisiae DNA ligase, and investigated its transcriptional regulation both as a function of cell cycle stage and after UV irradiation. The steady-state level of DNA ligase mRNA increases at least fourfold in late G1, after the completion of start but before S...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.1.226
更新日期:1985-01-01 00:00:00
abstract::Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine migh...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.9.3159-3165.2001
更新日期:2001-05-01 00:00:00
abstract::We have constructed a genomic DNA library from a methotrexate-resistant Chinese hamster ovary cell line (CHOC 400) in the cosmid vector pHC79. By utilizing a murine dihydrofolate reductase (DHFR) cDNA clone, we have identified 66 DHFR+ clones among the 11,000 colonies screened by colony hybridization. To isolate a rec...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.7.1266
更新日期:1983-07-01 00:00:00
abstract::Various stresses activate the c-Jun N-terminal kinase (JNK), which is involved in the regulation of many aspects of cellular physiology, including apoptosis. Here we demonstrate that in contrast to UV irradiation, heat shock causes little or no stimulation of the JNK-activating kinase SEK1, while knocking out the SEK1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2547
更新日期:1999-04-01 00:00:00
abstract::Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of a DNA-binding domain, FH...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00636-16
更新日期:2017-05-02 00:00:00
abstract::IMP dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthesis of guanine nucleotides. It is a target of therapeutically useful drugs and is implicated in the regulation of cell growth rate. In the yeast Saccharomyces cerevisiae, mutations in components of the RNA polymerase II (Pol II) transcription e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.20.7427-7437.2000
更新日期:2000-10-01 00:00:00
abstract::Drosophila melanogaster telomeres have two DNA domains: a terminal array of retrotransposons and a subterminal repetitive telomere-associated sequence (TAS), a source of telomere position effect (TPE). We reported previously that deletion of the 2L TAS array leads to dominant suppression of TPE by stimulating in trans...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00515-07
更新日期:2007-07-01 00:00:00
abstract::Mutations in the SRA1 or SRA3 gene eliminate the requirement for either RAS gene (RAS1 or RAS2) in Saccharomyces cerevisiae. We cloned SRA1 and SRA3 and determined their DNA sequences. SRA1 encodes the regulatory subunit of the cyclic AMP (cAMP)-dependent protein kinase and therefore is identical to REG1 and BCY1. Thi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.8.2653
更新日期:1987-08-01 00:00:00