Deregulated expression of cyclin D1 and other cell cycle-related genes in carcinogen-induced rat mammary tumors

Sgambato, Alessandro; Han, Edward K.; Zhang, Yujing; Moon, Richard C.; Santella, Regina M.; Weinstein, I B

doi:10.1093/carcin/16.9.2193

Cited by 55 publications

(36 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study also supports previous reports of deregulated expression and ampli®cation of cyclin D1 in chemically induced skin tumors (Bianchi et al, 1993;Mitsunaga et al, 1995;Robles and Conti, 1995), human tumors (Bartkova et al, 1995a,b;Wang et al, 1996;Weinstat-Saslow et al, 1995) and in rat mammary tumors (Sgambato et al, 1995). Overexpression of cyclin D1 in the mammary glands of transgenic mice leads to hyperplasia and tumor formation (Wang et al, 1994).…”

Section: Discussionsupporting

confidence: 91%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

View full text Add to dashboard Cite

It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16 Ink4a , p57 Kip2 ) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at speci®c times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.

show abstract

Section: Discussionsupporting

confidence: 91%

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

et al. 1998

View full text Add to dashboard Cite

show abstract

“…17 Cyclin D1 is overexpressed in rat mammary gland cancers induced by a variety of carcinogens, including DMBA, NMU and PhIP. 7,9,18 In light of the findings, it appears likely that cyclin D1 overexpression plays a central role in the development of chemically induced rat mammary gland carcinogenesis. The mechanisms for the upregulation of cyclin D1 in the rat mammary gland are not yet known, but several factors have been shown to regulate cyclin D1 gene expression.…”

Section: Discussionmentioning

confidence: 97%

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Papaconstantinou

Shanmugam

Shan

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Identification of molecular markers of early‐stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12‐dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real‐time PCR, RT‐PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of β‐casein and transferrin and higher expression of hsp27 in glands from DMBA‐treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki‐67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, α‐tubulin and hsp27, were all overexpressed in the mammary gland of DMBA‐treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley‐Liss, Inc.

show abstract

“…After G1, cells become largely independent of extracellular signals and progress automatically through subsequent cell cycle to the G1 phase (Pardee, 1989). There is increasing evidence that several types of experimental animal and human tumors display abnormalities in cell cycle regulatory genes (Bianchi et al, 1993;Kawamata et al, 1995;Sgambato et al, 1995;Landberg et al, 1997;Balasubramanian et al, 1998). Therefore we examined the protein expression of G1 cyclins and their associated cdks during UVBinduced phtocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse

et al. 1999

View full text Add to dashboard Cite

Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVBinduced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm 2 UVB radiation, thrice weekly for 24 weeks. The animals were sacri®ced at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any signi®cant change in UVB exposed skin, but signi®cant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle.

show abstract

Deregulated expression of cyclin D1 and other cell cycle-related genes in carcinogen-induced rat mammary tumors

Cited by 55 publications

References 0 publications

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Deregulated expression of cell-cycle proteins during premalignant progression in SENCAR mouse skin

Gene expression profiling in the mammary gland of rats treated with 7,12‐dimethylbenz[a]anthracene

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse

Contact Info

Product

Resources

About