Cyclin D1 activity regulates autophagy and senescence in the mammary epithelium.

Abstract:

:Overexpression of cyclin D1 is believed to endow mammary epithelial cells (MEC) with a proliferative advantage by virtue of its contribution to pRB inactivation. Accordingly, abrogation of the kinase-dependent function of cyclin D1 is sufficient to render mice resistant to breast cancer initiated by ErbB2. Here, we report that mouse cyclin D1(KE/KE) MECs (deficient in cyclin D1 activity) upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo. In addition, immortalized cyclin D1(KE/KE) MECs retain high rates of autophagy and reduced ErbB2-mediated transformation in vitro. However, highlighting its dual role during tumorigenesis, downregulation of autophagy led to an increase in senescence in cyclin D1(KE/KE) MECs. Autophagy upregulation was also confirmed in human mammary epithelial cells (HMEC) subjected to genetic and pharmacologic inhibition of cyclin D1 activity and, similar to our murine system, simultaneous inhibition of Cdk4/6 and autophagy in HMECs enhanced the senescence response. Collectively, our findings suggest a previously unrecognized function of cyclin D1 in suppressing autophagy in the mammary epithelium.

journal_name

Cancer Res

journal_title

Cancer research

authors

Brown NE,Jeselsohn R,Bihani T,Hu MG,Foltopoulou P,Kuperwasser C,Hinds PW

doi

10.1158/0008-5472.CAN-11-4139

subject

Has Abstract

pub_date

2012-12-15 00:00:00

pages

6477-89

issue

24

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-11-4139

journal_volume

72

pub_type

杂志文章
  • The Inhibitor of Apoptosis Protein Livin Confers Resistance to Fas-Mediated Immune Cytotoxicity in Refractory Lymphoma.

    abstract::Death receptor Fas-mediated apoptosis not only eliminates nonspecific and autoreactive B cells but also plays a major role in antitumor immunity. However, the possible mechanisms underlying impairment of Fas-mediated induction of apoptosis during lymphomagenesis remain unknown. In this study, we employed our developed...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-3993

    authors: Sugihara E,Hashimoto N,Osuka S,Shimizu T,Ueno S,Okazaki S,Yaguchi T,Kawakami Y,Kosaki K,Sato TA,Okamoto S,Saya H

    更新日期:2020-10-15 00:00:00

  • Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo.

    abstract::Hedgehog (Hh) and transforming growth factor-beta (TGF-beta) family members are involved in numerous overlapping processes during embryonic development, hair cycle, and cancer. Herein, we show that TGF-beta induces the expression of the Hh signaling molecules Gli1 and Gli2 in various human cell types, including normal...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0491

    authors: Dennler S,André J,Alexaki I,Li A,Magnaldo T,ten Dijke P,Wang XJ,Verrecchia F,Mauviel A

    更新日期:2007-07-15 00:00:00

  • Identification and biological evaluation of a novel and potent small molecule radiation sensitizer via an unbiased screen of a chemical library.

    abstract::For patients with solid tumors, the tolerance of surrounding tissues often limits the dose of radiation that can be delivered. Thus, agents that preferentially increase the cytotoxic effects of radiation toward tumor cells would significantly alter the therapeutic ratio and improve patient survival. Using a high-throu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0477

    authors: Lally BE,Geiger GA,Kridel S,Arcury-Quandt AE,Robbins ME,Kock ND,Wheeler K,Peddi P,Georgakilas A,Kao GD,Koumenis C

    更新日期:2007-09-15 00:00:00

  • Macrophage content of spontaneous metastases at different stages of growth.

    abstract::The macrophage content of spontaneous metastases has been quantified morphometrically for a panel of rodent tumors at different stages of metastatic tumor growth. Using a histochemical technique to selectively stain macrophages, we have evaluated the relative content of macrophages in spontaneous pulmonary metastases ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bugelski PJ,Corwin SP,North SM,Kirsh RL,Nicolson GL,Poste G

    更新日期:1987-08-01 00:00:00

  • Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells.

    abstract::Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-4653

    authors: Dimitroff CJ,Descheny L,Trujillo N,Kim R,Nguyen V,Huang W,Pienta KJ,Kutok JL,Rubin MA

    更新日期:2005-07-01 00:00:00

  • Comparison of the effects of three different toxin genes and their levels of expression on cell growth and bystander effect in lung adenocarcinoma.

    abstract::Transduction of malignant cells with toxin genes provides a novel means to promote tumor cell destruction. The efficacy of a toxin gene is dependent on the cell type targeted, the quantity of exogenous protein synthesized, and the mechanisms of growth inhibition and bystander killing. To develop gene therapy for targe...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hoganson DK,Batra RK,Olsen JC,Boucher RC

    更新日期:1996-03-15 00:00:00

  • Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a Phase I trial.

    abstract::The serum half-life of 5-fluorouracil (5-FUra) in humans is best described as a biexponential decay function, with t1/2 alpha = 7.8 +/- 2.6 (S.E.) min and t1/2 beta = 36.8 +/- 13.5 min during initial courses of this drug alone. Pharmacokinetics of 5-FUra during courses of daily therapy (for 5 days) revealed prolongati...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kirkwood JM,Ensminger W,Rosowsky A,Papathanasopoulos N,Frei E 3rd

    更新日期:1980-01-01 00:00:00

  • Loss of p16INK4 expression by methylation is associated with lifespan extension of human mammary epithelial cells.

    abstract::Inactivation of p16INK4 tumor suppressor gene function is frequently observed in breast cancer. We examined p16INK4 expression in human mammary epithelial cell (HMEC) cultures established from four normal donors. Normal HMECs divide a limited number of times before proliferation ceases in a state referred to as select...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Huschtscha LI,Noble JR,Neumann AA,Moy EL,Barry P,Melki JR,Clark SJ,Reddel RR

    更新日期:1998-08-15 00:00:00

  • Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells.

    abstract::Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Ther...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3105

    authors: Miki Y,Suzuki T,Tazawa C,Yamaguchi Y,Kitada K,Honma S,Moriya T,Hirakawa H,Evans DB,Hayashi S,Ohuchi N,Sasano H

    更新日期:2007-04-15 00:00:00

  • Activation of HIF2α in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis.

    abstract::Renal cell carcinoma (RCC) is the most common primary cancer arising from the kidney in adults, with clear cell renal cell carcinoma (ccRCC) representing approximately 75% of all RCCs. Increased expression of the hypoxia-induced factors-1α (HIF1α) and HIF2α has been suggested as a pivotal step in ccRCC carcinogenesis,...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-3983

    authors: Fu L,Wang G,Shevchuk MM,Nanus DM,Gudas LJ

    更新日期:2013-05-01 00:00:00

  • TSP50 encodes a testis-specific protease and is negatively regulated by p53.

    abstract::Earlier studies suggested that TSP50 is a testis-specific gene that encodes a protein, which is homologous to serine proteases but differs in that threonine replaces serine in its catalytic triad. Most importantly, it was abnormally reactivated in many breast cancer biopsies tested. While further investigating its bio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3688

    authors: Xu H,Shan J,Jurukovski V,Yuan L,Li J,Tian K

    更新日期:2007-02-01 00:00:00

  • Toll-like receptors 3 and 7 agonists enhance tumor cell lysis by human gammadelta T cells.

    abstract::Toll-like receptor (TLR) agonists are considered adjuvants in clinical trials of cancer immunotherapy. Here, we investigated the modulation of gammadelta T cell-mediated tumor cell lysis by TLR ligands. gammadelta T-cell cytotoxicity and granzyme A/B production were enhanced after pretreatment of tumor cells with TLR3...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-1602

    authors: Shojaei H,Oberg HH,Juricke M,Marischen L,Kunz M,Mundhenke C,Gieseler F,Kabelitz D,Wesch D

    更新日期:2009-11-15 00:00:00

  • Ultraviolet-specific mutations in p53 gene in skin tumors in xeroderma pigmentosum patients.

    abstract::Mutations in the p53 gene were identified in five of eight non-melanoma skin tumors in the sun-exposed areas of xeroderma pigmentosum patients by the polymerase chain reaction and single strand conformation polymorphism analysis followed by sequencing of the DNA. All mutations occurred at the dipyrimidine sites, indic...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Sato M,Nishigori C,Zghal M,Yagi T,Takebe H

    更新日期:1993-07-01 00:00:00

  • Phenotypic characterization of metaplastic intestinal glands and ductular hepatocytes in cholangiofibrotic lesions rapidly induced in the caudate liver lobe of rats treated with furan.

    abstract::In order to investigate the early cellular changes in liver associated with furan cholangiocarcinogenesis, young adult male Fischer 344 rats were administered furan by gavage once a day, 5 days a wk for 2 to 3 wk at doses ranging from 15 to 60 mg/kg of body weight per day. The most conspicuous feature observed in the ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Elmore LW,Sirica AE

    更新日期:1991-10-15 00:00:00

  • SOX9 is expressed in normal prostate basal cells and regulates androgen receptor expression in prostate cancer cells.

    abstract::SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family of HMG DNA-binding domain transcription factors and is required for the development and differentiation of multiple cell lineages. This report shows that basal epithelial cells express SOX9 in normal prostate, with no detectable expression ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-1672

    authors: Wang H,McKnight NC,Zhang T,Lu ML,Balk SP,Yuan X

    更新日期:2007-01-15 00:00:00

  • Interspecies scaling of the pharmacokinetics of N-nitrosodimethylamine.

    abstract::The pharmacokinetics of N-nitrosodimethylamine was studied in patas monkeys following i.v. doses of 0.5, 1.0, and 5.0 mg/kg and a p.o. dose of 1.0 mg/kg, and in Swiss mice at i.v. doses of 1.0 and 2.0 mg/kg. In the patas monkey the pharmacokinetics was linear over the i.v. dose range studied. The mean clearance (Cl), ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gombar CT,Harrington GW,Pylypiw HM Jr,Anderson LM,Palmer AE,Rice JM,Magee PN,Burak ES

    更新日期:1990-07-15 00:00:00

  • Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence following Radiotherapy in Immunosuppressed Patients.

    abstract::Although radiotherapy (RT) decreases the incidence of locoregional recurrence in breast cancer, patients with triple-negative breast cancer (TNBC) have increased risk of local recurrence following breast-conserving therapy. The relationship between RT and local recurrence is unknown. Here, we tested the hypothesis tha...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-3623

    authors: Rafat M,Aguilera TA,Vilalta M,Bronsart LL,Soto LA,von Eyben R,Golla MA,Ahrari Y,Melemenidis S,Afghahi A,Jenkins MJ,Kurian AW,Horst KC,Giaccia AJ,Graves EE

    更新日期:2018-08-01 00:00:00

  • Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts.

    abstract::Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade of CSF-1 would be beneficial in breast cancer treatment, we developed a murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against mouse (ho...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3523

    authors: Paulus P,Stanley ER,Schäfer R,Abraham D,Aharinejad S

    更新日期:2006-04-15 00:00:00

  • Isolation of a prostate carcinoma cell proliferation-inhibiting factor from human seminal plasma and its similarity to transforming growth factor beta.

    abstract::Human seminal plasma (SP) has been known to contain both growth-inhibitory and -stimulatory factors. We attempted to identify a factor that inhibited DNA synthesis in some metastatic prostate cancer cell lines. The SP factor was sensitive to digestion by trypsin, but its activity increased after boiling or dialysis ag...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lokeshwar BL,Block NL

    更新日期:1992-10-15 00:00:00

  • Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma.

    abstract::Taxol is a novel antitumor agent with demonstrated efficacy against ovarian, breast, and non-small cell lung cancers in Phase II clinical trials, but which has been shown not to cross the blood-brain barrier. To adapt taxol as a therapy for brain tumors, we have incorporated it into a biodegradable polyanhydride matri...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Walter KA,Cahan MA,Gur A,Tyler B,Hilton J,Colvin OM,Burger PC,Domb A,Brem H

    更新日期:1994-04-15 00:00:00

  • Inflammation in the genesis and perpetuation of cancer: summary and recommendations from a national cancer institute-sponsored meeting.

    abstract::The Inflammation and Cancer Think Tank Meeting was organized by the National Cancer Institute with the purpose of identifying research advances, gaps, and opportunities for the study and clinical application of the role of inflammation on tumorigenesis. The format of this meeting consisted of brief presentations that ...

    journal_title:Cancer research

    pub_type:

    doi:10.1158/0008-5472.CAN-05-1777

    authors: Peek RM Jr,Mohla S,DuBois RN

    更新日期:2005-10-01 00:00:00

  • Anti-GM2 monoclonal antibodies induce necrosis in GM2-rich cultures of a human glioma cell line.

    abstract::The effects of four anti-GM2 monoclonal antibodies (DMAb-1, DMAb-2, DMAb-3, and DMAb-5) were studied on spheroid cultures from a human glioma cell line (D-54 MG) that is known to express high levels of GM2. The spheroids developed central necrosis 48 h after antibody exposures at concentrations greater than 6 microgra...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bjerkvig R,Engebraaten O,Laerum OD,Fredman P,Svennerholm L,Vrionis FD,Wikstrand CJ,Bigner DD

    更新日期:1991-09-01 00:00:00

  • Cytotoxicity of thioether-lysophospholipids in leukemias and tumors of human origin.

    abstract::Thioether-lysophospholipids inhibited the in vitro incorporation of [3H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning ele...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Berdel WE,Fromm M,Fink U,Pahlke W,Bicker U,Reichert A,Rastetter J

    更新日期:1983-11-01 00:00:00

  • Ganglioside GD1alpha functions in the adhesion of metastatic tumor cells to endothelial cells of the target tissue.

    abstract::We studied the role of glycosphingolipids expressed on the cell surfaces of a metastatic tumor cell line. Glycosphingolipid compositions of the low-metastatic murine lymphosarcoma cell line RAW117-P and its sub-line, RAW117-H10, which shows higher metastatic potential for the liver than P cells, were compared. Both ty...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Taki T,Ishikawa D,Ogura M,Nakajima M,Handa S

    更新日期:1997-05-15 00:00:00

  • The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma.

    abstract::Partial regression in cutaneous malignant melanoma has been reported by a number of observers, albeit not all, to be associated with a relatively poor prognosis; in contrast, a keratoacanthoma, which eventually regresses, does not metastasize. The Hammond effect could explain the possibly poor prognosis of the thin re...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:

    authors: Prehn RT

    更新日期:1996-03-01 00:00:00

  • Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

    abstract::Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extrace...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-1862

    authors: McIntyre A,Hulikova A,Ledaki I,Snell C,Singleton D,Steers G,Seden P,Jones D,Bridges E,Wigfield S,Li JL,Russell A,Swietach P,Harris AL

    更新日期:2016-07-01 00:00:00

  • Selective antitumor effect of novel protease-mediated photodynamic agent.

    abstract::A new approach to selective photodynamic therapy (PDT) was developed by designing chlorin e6 (Ce6)-containing macromolecules, which are sensitive to tumor-associated proteases. The agents are nontoxic in their native state but become fluorescent and produce singlet oxygen on protease conversion. Coupled with optimized...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0448

    authors: Choi Y,Weissleder R,Tung CH

    更新日期:2006-07-15 00:00:00

  • Sensitivities of monolayers and spheroids of the human bladder cancer cell line MGH-U1 to the drugs used for intravesical chemotherapy.

    abstract::The in vitro cytotoxicities of the four drugs most frequently used for intravesical chemotherapy (Adriamycin, epodyl, mitomycin C, Thiotepa) and epirubicin were compared using monolayers and multicellular tumor spheroids of the human bladder cancer cell line, MGH-U1. Adriamycin and epirubicin were most cytotoxic again...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Knuchel R,Hofstadter F,Jenkins WE,Masters JR

    更新日期:1989-03-15 00:00:00

  • Amplification of cyclin genes in colorectal carcinomas.

    abstract::The genetic status of cyclin genes was examined in a panel of 47 colorectal carcinoma cell lines. Cyclin D2 was found to be amplified in one tumor and cyclin E in another. In each of the two cases, the amplified cyclin gene was overexpressed at the protein or mRNA level. Cyclin D1, previously shown to be amplified in ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Leach FS,Elledge SJ,Sherr CJ,Willson JK,Markowitz S,Kinzler KW,Vogelstein B

    更新日期:1993-05-01 00:00:00

  • Complete regression of experimental solid tumors by combination LEC/chTNT-3 immunotherapy and CD25(+) T-cell depletion.

    abstract::LEC/chTNT-3, a chemokine fusion protein generated previously in our laboratory, produces a 40-60% reduction in well-established solid tumors of the BALB/c mouse. In this study, CD25(+) T-cell depletion was used in combination with LEC/chTNT-3 treatment to enhance the therapeutic value of this approach. In two tumor mo...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Li J,Hu P,Khawli LA,Epstein AL

    更新日期:2003-12-01 00:00:00