Bmi-1 cooperates with human papillomavirus type 16 E6 to immortalize normal human oral keratinocytes

Kim, Reuben H.; Kang, Mo K.; Shin, Kihyuk; Oo, Zin Mar; Han, Thomas J.; Baluda, M A; Park, No‐Hee

doi:10.1016/j.yexcr.2006.10.025

Cited by 42 publications

(60 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, we compared the relative telomere lengths in NHEK before and after EMT by the qPCR method. HOK-16B, an immortalized counterpart of NHOK (39), demonstrated lower telomere length compared with NHEK, consistent with our prior report (40) (Fig. 7D).…”

Section: Transduction Of ⌬Np63␣supporting

confidence: 92%

“…This is in contrast to a recent study showing that Bmi-1 alone is capable of inducing EMT in nasopharyngeal epithelial cells (53). Long term culture of NHOK was maintained after Bmi-1 transduction, but no sign of EMT was ever noted, even during cellular immortalization with Bmi-1 and human papillomavirus E6 (40). These data indicate that cells do respond differently to Bmi-1 transduction based on tissue origin.…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

ΔNp63α Protein Triggers Epithelial-Mesenchymal Transition and Confers Stem Cell Properties in Normal Human Keratinocytes

Kim

Shin

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: ⌬Np63␣ is an isoform of p63 that is predominantly expressed in normal epidermis. Results: Retroviral transduction of ⌬Np63␣ into rapidly proliferating primary human epidermal keratinocytes led to epithelialmesenchymal transition (EMT) and acquisition of stemlike properties. Conclusion: ⌬Np63␣ regulates EMT in primary human keratinocytes in a TGF-␤-dependent manner. Significance: Altering p63 level in NHEK may be a novel method to generate "induced mesenchymal stem cells" with multipotent capacity.

show abstract

Section: Transduction Of ⌬Np63␣supporting

confidence: 92%

Section: Discussionmentioning

confidence: 84%

ΔNp63α Protein Triggers Epithelial-Mesenchymal Transition and Confers Stem Cell Properties in Normal Human Keratinocytes

Kim

Shin

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The inverse correlation between Bmi-1 and p16 INK4A protein expression levels was not evident in the OSCC cell lines in our study ( Figure 1B). Furthermore, we recently reported that expression of exogenous Bmi-1 in NHOK led to significant extension (2.7 fold) of replicative life span but did not efficiently downregulate the expression of p16 INK4A (Kim et al, 2006). It is possible that Bmi-1 targets other important regulators of cell division in NHOK, such as p14 ARF or p15 INK4B , as previously suggested (Jacobs et al, 1999).…”

Section: Discussionmentioning

confidence: 84%

Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival

Mk¹,

Kim²,

Sj³

et al. 2006

Br J Cancer

142

125

View full text Add to dashboard Cite

Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study was undertaken to determine the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression levels were markedly enhanced in the cells of oral squamous cell carcinomas (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi-1 expression was also detected in situ in the archived oral mucosal tissues with cancerous and precancerous histopathology, including that of mild epithelial dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation, endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK by RNA interference. After Bmi-1 knockdown, cell replication was severely retarded. However, the expression of p16 INK4A , a known cellular target of Bmi-1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1 knockdown in HOK-16B-BaP-T cells, in which the p16 INK4A /pRb pathway was abrogated, led to immediate arrest of replication and loss of viable cells. Thus, our data suggest that Bmi-1 may act through p16 INK4A -independent pathways to regulate cellular proliferation during oral cancer progression.

show abstract

“…By downregulating p16 INK4A and ARF, Bmi-1 can potentially regulate p16-pRb and p53-p21 pathways of senescence (20). Indeed, overexpression of Bmi-1 bypasses senescence in human and rodent fibroblasts, human mammary epithelial cells (HMEC), nasopharyngeal epithelial cells, and normal oral keratinocytes (11,18,19,21,22). Along these lines, we have recently reported that Bmi-1 down-regulation by another PcG protein Mel-18, and Bmi-1 knockdown using an RNA interference approach induces premature senescence via up-regulation of p16…”

Section: Introductionmentioning

confidence: 99%

Bmi-1 Cooperates with H-Ras to Transform Human Mammary Epithelial Cells via Dysregulation of Multiple Growth-Regulatory Pathways

Datta¹,

Hoenerhoff

Bommi³

et al. 2007

Cancer Research

View full text Add to dashboard Cite

Elevated expression of Bmi-1 is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic transformation. However, Bmi-1 co-overexpression with activated H-Ras (RasG12V) resulted in efficient transformation of MCF10A cells in vitro. Although early-passage H-Ras-expressing MCF10A cells were not transformed, late-passage H-Ras-expressing cells exhibited features of transformation in vitro. Early-and late-passage H-Ras-expressing cells also differed in levels of expression of H-Ras and Ki-67, a marker of proliferation. Subsets of earlypassage H-Ras-expressing cells exhibited high Ras expression and were negative for Ki-67, whereas most late-passage H-Ras-expressing cells expressed low levels of Ras and were Ki-67 positive. Injection of late-passage H-Ras-expressing cells in severe combined immunodeficient mice formed carcinomas with leiomatous, hemangiomatous, and mast cell components; these tumors were quite distinct from those induced by latepassage cells co-overexpressing Bmi-1 and H-Ras, which formed poorly differentiated carcinomas with spindle cell features. Bmi-1 and H-Ras co-overexpression in MCF10A cells also induced features of epithelial-to-mesenchymal transition. Importantly, Bmi-1 inhibited senescence and permitted proliferation of cells expressing high levels of Ras. Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes HMEC transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways by p16INK4a -independent mechanisms. [Cancer Res 2007;67(21):10286-95]

show abstract

Bmi-1 cooperates with human papillomavirus type 16 E6 to immortalize normal human oral keratinocytes

Cited by 42 publications

References 48 publications

ΔNp63α Protein Triggers Epithelial-Mesenchymal Transition and Confers Stem Cell Properties in Normal Human Keratinocytes

ΔNp63α Protein Triggers Epithelial-Mesenchymal Transition and Confers Stem Cell Properties in Normal Human Keratinocytes

Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival

Bmi-1 Cooperates with H-Ras to Transform Human Mammary Epithelial Cells via Dysregulation of Multiple Growth-Regulatory Pathways

Contact Info

Product

Resources

About