Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis

Ise, Kazuhiro; Nakamura, Kenji; Nakao, Kazuki; Shimizu, Seiichiro; Harada, Hosami; Ichise, Taeko; Miyoshi, Jun; Gondo, Yoichi; Ishikawa, Takatoshi; Aiba, Atsu; Katsuki, Motoya

doi:10.1038/sj.onc.1203600

Cited by 120 publications

(111 citation statements)

References 25 publications

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“…The phenotypes of Hras, N-ras and K-ras knockout mice indicate clear distinctions in function and/or expression among the family members. H-ras and N-ras knockout mice are viable with no overt abnormalities (Umanoff et al, 1995;Ise et al, 2000). In contrast, K-ras knockout mice die at 12.5 days post coitus (p.c.)…”

Section: Discussionmentioning

confidence: 99%

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice

et al. 2006

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Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53. To investigate their possible involvement in the tumorigenesis, we generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by Cre/LoxP system on a background of p53 alteration. Electroporation of Cre expression vector in skeletal muscle tissues resulted in the generation of tumor in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53 À/À and p53 À/ þ backgrounds, respectively. The tumor histology was pleomorphic RMS with characteristic bizarre giant cells, positive for desmin and a-sarcomeric actin and exhibiting remarkable increase in total and phosphorylated extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild-type p53 was detected in K-rasG12V-expressed tumors of p53 À/ þ mice. Early lesions 3 weeks after electroporation consisted of proliferating populations of myogenic progenitors, including stem cells positive for ScaI antigen, immature cells positive for desmin and neural cell adhesion molecule-positive myotubes. Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the development of pleomorphic RMS in adult mice, providing a useful mouse model for further detailed studies.

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Section: Discussionmentioning

confidence: 99%

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice

et al. 2006

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“…Furthermore, the functional activity of Ras is now known to be required for mitogenic signaling by most growth factor receptors (Ise et al, 2000). In contrast, the diversity of biological functions performed by small GTPases of the Rho family is just beginning to be fully appreciated.…”

Section: Discussionmentioning

confidence: 99%

Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-κB

et al. 2002

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“…As a leading step, 'initiation' causes gene mutations (predominantly Hras1 gene) in epidermal keratinocytes in response to chemical mutagen exposure, which is often polycyclic aromatic hydrocarbon such as 7,12-dimethylbenz [α] anthracene (DMBA) (Ise et al, 2000;Abel et al, 2009). This step is irreversible and produces no visible tumor until repeated application of tumor promoting agent such as 12-O-tetradecanoylphorbol-13-acetate (TPA) takes place.…”

Section: Isolation Of a Quinone-rich Fraction From Ardisia Crispa Roomentioning

confidence: 99%

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

Yeong

Hamid²,

Yazan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(α)anthracene (DMBA, 100 µg/100 µl) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/ promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume (8.79±5.44) and tumor burden (3.60±1.17). Comparatively, group III revealed only 20% of tumor incidence, tumor burden (3.00±1.00) and tumor volume (2.40±1.12), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

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Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis

Cited by 120 publications

References 25 publications

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice

Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-κB

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

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