Ppp6c deletion promotes mutated RAS-initiated tumor formation in keratinocytes.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19745
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: INOUE Yui 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 共同研究員 (30750442)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: プロテインホスファターゼ / Kras

Outline of Final Research Achievements

To assess effects of PP6 loss on activated K-ras-induced tumorigenesis in keratinocytes, we established K14-CreERtam/LSL-K-rasG12D/Ppp6cflox/flox mice (exhibiting epidermal-specific tamoxifen-inducible K-rasG12D expression plus Ppp6c deficiency) and K14-CreERtam/LSL-K-rasG12D mice (which showed only epidermal-specific tamoxifen-inducible K-rasG12D expression). Ten independent 4HT-treated K14-CreERtam/LSL-K-rasG12D/Ppp6cflox/flox mice developed lip tumors. Microscopic analysis of lip tumor tissue from the mouse indicated hyperkeratotic papillomatous proliferative lesions. It is noteworthy that a region of squamous cell carcinoma in situ (CIS) sacrificed between days 16 to 20. To examine lip epidermis growth, we measured tissue thickness at 4, 8 and 12 days after 4HT injection. The ratio of lip thickness of K14-CreERtam/LSL-K-rasG12D/Ppp6cflox/flox to that of K14-CreERtam/LSL-K-rasG12D mice was 2.3, 24 and 42, at days 4, 8 and 12, respectively.

Free Research Field

医歯薬学