Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.

Gavrieli, Yael; Sherman, Yoav; Ben‐Sasson, Shmuel A.

doi:10.1083/jcb.119.3.493

Cited by 8,878 publications

(5,208 citation statements)

References 31 publications

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“…TUNEL is a sensitive and quantitative method for the detection of 3Ј-OH ends generated by endonuclease-mediated DNA strand breaks. 29 Figure 6 shows a flow cytometric analysis of cells from the C9 clone carrying antisense IGF-IR. There is a peak on the histogram (Fig 6A, right panel) that indicates that ϳ59% of the cells from the C9 clone carrying antisense IGF-IR are apoptotic.…”

Section: Resultsmentioning

confidence: 99%

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

Chernicky

Tan

et al. 2000

Cancer Gene Ther

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The type I insulin-like growth factor receptor (IGF-IR) plays an important role in the growth and transformation of breast cancer cells. In this study, we investigated the effects of treatment with an antisense IGF-IR construct on cells from the highly metastatic estrogen receptor-negative human breast cancer cell line MDA-MB-435s. The cells carrying the antisense IGF-IR had a markedly reduced expression of IGF-IR, had a significant decrease in cell proliferation, and lost the ability to form colonies in soft agar. There was a delay in tumor formation and a dramatic reduction in tumor size when cells carrying the antisense IGF-IR were injected into either nude or severe combined immunodeficient (scid) beige mice. We have also provided data that show that the scid beige mouse is a more suitable model for studying metastasis of the MDA-MB-435s cells. All of the scid beige mice injected with cells carrying the control construct had metastasis to the lungs, whereas lungs from the nude mice had no apparent metastatic sites after 11 weeks. When cells carrying antisense IGF-IR were injected subcutaneously in scid beige mice, the animals had a significant increase in survival compared with mice injected with cells carrying the control construct. Taken together, these results indicate that the IGF-IR can play a critical role in the progression of breast cancer. Our studies provide a basis for the development of future treatment strategies targeting the IGF-IR in metastatic breast cancer. Cancer Gene Therapy (2000) 7, 384 -395

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Section: Resultsmentioning

confidence: 99%

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

Chernicky

Tan

et al. 2000

Cancer Gene Ther

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“…Mitotic activity ceases as cells migrate out of the crypts, and there is a concomitant increase in the expression of a number of di erentiated gene products (Gordon et al, 1992;Traber, 1994). Di erentiated enterocytes are removed by the process of apoptosis which occurs throughout the villus and by exfoliation which occurs at the villus tip (Gavrieli et al, 1992;Hall et al, 1994;Chandrasekaran et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 effects on proliferation of rat intestinal epithelial cells are due to inhibition of cyclin D1 expression

Sakai

et al. 1998

Oncogene

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Transforming growth factor-beta 1 (TGF-b1) arrests intestinal epithelial cells (RIE-1 and IEC-6) in the G1 phase of the cell cycle and inhibits cyclin D1 expression. This report describes experiments designed to elucidate the mechanism of cyclin D1 inhibition and to determine whether inhibition of cyclin D1 expression is the cause, rather than the result, of TGF-b1-mediated cell cycle arrest. TGF-b1 inhibition of IEC-6 cell proliferation was associated with a decrease in the abundance of cyclin D1/Cdk4 complexes and a corresponding decrease in Cdk4-dependent phosphorylation of the retinoblastoma protein. Metabolic labeling studies indicated that TGFb1 inhibited cyclin D1 synthesis without altering the rate of cyclin D1 protein degradation. Cyclin D1 antisense oligonucleotides blocked serum-stimulated induction of cyclin D1 and DNA synthesis, whereas cyclin D1 sense oligonucleotides had no e ect. RIE-1 cells were engineered to overexpress human cyclin D1 under the control of a tetracycline-repressible promoter. These cells entered S phase in the presence of TGF-b1 only when human cyclin D1 was derepressed by the withdrawal of tetracycline. These data indicate that TGF-b1 inhibits the synthesis of cyclin D1 in gut epithelial cells and that this inhibition is the cause, rather than the result, of TGF-b1-mediated arrest of intestinal epithelial cell proliferation.

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“…Nevertheless, we considered whether keratinocyte apoptosis could account for decreased outgrowth from ESGs in aged skin. We thus assessed a potential increase in apoptotic keratinocytes during aged skin repair in situ via specific labeling of nuclear DNA fragmentation (Gavrieli et al ., 1992). We detected apoptotic cells in the scab of young and aged wounded samples as expected (apoptosis may appear different in these young and aged scabs but we did not collect enough samples with intact scabs to ascertain this possibility).…”

Section: Resultsmentioning

confidence: 99%

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin

et al. 2016

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SummaryHuman skin heals more slowly in aged vs. young adults, but the mechanism for this delay is unclear. In humans, eccrine sweat glands (ESGs) and hair follicles underlying wounds generate cohesive keratinocyte outgrowths that expand to form the new epidermis. Here, we compared the re‐epithelialization of partial‐thickness wounds created on the forearm of healthy young (< 40 yo) and aged (> 70 yo) adults. Our results confirm that the outgrowth of cells from ESGs is a major feature of repair in young skin. Strikingly, in aged skin, although ESG density is unaltered, less than 50% of the ESGs generate epithelial outgrowths during repair (vs. 100% in young). Surprisingly, aging does not alter the wound‐induced proliferation response in hair follicles or ESGs. Instead, there is an overall reduced cohesiveness of keratinocytes in aged skin. Reduced cell–cell cohesiveness was most obvious in ESG‐derived outgrowths that, when present, were surrounded by unconnected cells in the scab overlaying aged wounds. Reduced cell–cell contact persisted during the repair process, with increased intercellular spacing and reduced number of desmosomes. Together, reduced outgrowths of ESG (i) reduce the initial number of cells participating in epidermal repair, (ii) delay wound closure, and (iii) lead to a thinner repaired epidermis in aged vs. young skin. Failure to form cohesive ESG outgrowths may reflect impaired interactions of keratinocytes with the damaged ECM in aged skin. Our findings provide a framework to better understand the mediators of delayed re‐epithelialization in aging and further support the importance of ESGs for the repair of human wounds.

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Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.

Cited by 8,878 publications

References 31 publications

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

TGF-β1 effects on proliferation of rat intestinal epithelial cells are due to inhibition of cyclin D1 expression

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin

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