p16/MTS1/INK4A suppresses prostate cancer by both pRb dependent and independent pathways

Steiner, Mitchell S.; Wang, Ying; Zhang, Yu; Zhang, Xiongwen; Lü, Yi

doi:10.1038/sj.onc.1203428

Cited by 42 publications

(33 citation statements)

References 54 publications

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“…Thus, expression of endogenous wild -type p53 contributes to Ad1b -mediated suppression of tumor cell growth and viability, but is not strictly required. Furthermore, because T98G cells lack expression of the cyclin-dependent kinase inhibitor, p16, 27 and therefore have a defective Rb pathway, and DU145 cells express a nonfunctional Rb protein, 30 these results suggest an activity of ARF in human tumor cell lines that is independent of either the p53 or Rb pathway.…”

Section: Cancer Gene Therapymentioning

confidence: 86%

Growth suppression by a p14ARF exon 1β adenovirus in human tumor cell lines of varying p53 and Rb status

et al. 2002

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We have analyzed the ability of an adenoviral vector encoding the exon 1b region of the p14 ARF tumor suppressor ( ARF ) to suppress the growth and viability of an array of tumor cell lines of various origins and varying p53 and Rb status, in order to establish the clinical potential of ARF. An important activity of ARF is regulation of p53 stability and function through binding to the mdm2 protein. By sequestering mdm2, ARF may promote growth suppression through the Rb pathway as well because mdm2 can bind to Rb and attenuate its function. Whereas the high frequency of ARF gene deletion in human cancers, accounting for some 40% of cancers overall, suggests that ARF would be a strong candidate for therapeutic application, the possible dependence of ARF activity on p53 and Rb function presents a potential limitation to its application, as these functions are often impaired in cancer. We show here that a replication -defective adenovirus, Ad1b, encoding the exon 1b region of ARF is most effective in tumor cells expressing endogenous wild -type p53. Nevertheless, Ad1b suppresses tumor cell growth and viability in vitro and in vivo, inducing G1 or G2 cell cycle arrest and cell death even in tumor cells lacking both functional Rb and p53 pathways, and independently of induction of the p53 downstream targets, p21, bax, and mdm2. These results point to an activity of ARF in human tumor cells that is independent of Rb or p53, and suggest that therapeutic applications based on ARF would have a broad clinical application in cancer.

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Section: Cancer Gene Therapymentioning

confidence: 86%

Growth suppression by a p14ARF exon 1β adenovirus in human tumor cell lines of varying p53 and Rb status

et al. 2002

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“…70 Although the PC-3, DU145, and LNCaP cell lines are the most popular human prostate cancer lines studied in this field, the PPC-1 line is the only one that is derived from a human primary prostate carcinoma rather from a metastasis of the primary prostate cancer (such as LNCaP, DU145, and PC-3). Therefore, results from the PPC-1 line may better reflect and represent the actual situation for the current approach of gene therapy (i.e., by direct intraprostatic injection of viral vector into the primary cancer site, the prostate).…”

Section: Discussionmentioning

confidence: 99%

Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence

et al. 2000

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“…DNA extraction and analysis of DNA fragmentation Soluble DNA was extracted as described previously (Steiner et al, 2000), with slight modifications. Briefly, the suspended cells in medium were collected 48 h after seeding to 100-mm plates.…”

Section: Wound Healing Assaysmentioning

confidence: 99%

C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells

Huang

et al. 2006

Oncogene

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Changes in carbohydrates on the cell surface are associated with tumor malignancy. The mucin-type core 2 b-1,6-N-acetylglucosaminyltransferase (C2GnT-M) is highly expressed in the gastrointestinal tract and catalyses the formation of core 2, core 4, and blood group I branches on O-glycans. In the present study, we evaluated the role of C2GnT-M in colorectal cancer. C2GnT-M downexpression was observed in 73.6% of the primary tumors from colorectal cancer patients (39 of 53) analysed by cancer profiling array. Consistently, the majority of colon cancer cell lines and primary colon tumors expressed lower levels of C2GnT-M than did normal colon tissues by RT-PCR. HCT116 cells stably transfected with C2GnT-M inhibited expression of the core 1 structure, Galb1,3GalNAca1-Ser/Thr, on the cell surface. Moreover, C2GnT-M expression suppressed cell adhesion, motility, and invasion as well as colony formation ability. The growth of C2GnT-M-transfected HCT116 and SW480 cells was dramatically suppressed, and the cell death induced by C2GnT-M was demonstrated by an increase in the annexin V-positive cells. Interestingly, C2GnT-M inhibited cell adhesion to collagen IV and fibronectin, and decreased tyrosine phosphorylation of paxillin, indicating that the changes in cancer behavior may be partly mediated by integrin-signaling pathways. Tumor growth in vivo was also significantly suppressed by C2GnT-M in the xenografts of nude mice. These results demonstrate that C2GnT-M is frequently downregulated in colorectal cancer and suppresses colon cancer cell growth.

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p16/MTS1/INK4A suppresses prostate cancer by both pRb dependent and independent pathways

Cited by 42 publications

References 54 publications

Growth suppression by a p14ARF exon 1β adenovirus in human tumor cell lines of varying p53 and Rb status

Growth suppression by a p14ARF exon 1β adenovirus in human tumor cell lines of varying p53 and Rb status

Adenoviral vector containing wild-type p16 suppresses prostate cancer growth and prolongs survival by inducing cell senescence

C2GnT-M is downregulated in colorectal cancer and its re-expression causes growth inhibition of colon cancer cells

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