Phenotypes for Cdk4 Tg(Mt1-Hgf)#Lmb MGI:6259566 MGI Mouse

increased incidence of tumors by chemical induction ( J:111992 )

• in a 2-step (DMBA/TPA) skin carcinogenesis protocol, all (16 of 16) mice show melanocytic nevi within the first weeks of life while still under TPA treatment

• all DMBA/TPA-treated mice develop widespread, rapidly growing skin melanomas and have to be sacrificed by 12 weeks of age due to melanomas >10 mm in diameter and systemic signs of illness; an average of ~48 cutaneous melanomas is observed

• DMBA/TPA-induced melanomas involve the epidermo-dermal junction and show vertical invasive growth into the dermis; at 12 weeks of age, vertical tumor thickness is larger than that in Cdk4^tm1.1Bbd/Cdk4⁺ Tg(Mt1-HGFSF)#Lmb/0 mice

• heavily pigmented epitheloid melanoma cells are arranged in bands and nests between lightly pigmented spindle-shaped melanoma cells

• only 3 of 16 DMBA/TPA-treated mice develop a single papilloma in skin

increased skin tumor incidence ( J:111992 )

• at 30 weeks of age, untreated mice exhibit a similar number of melanocytic nevi in skin as untreated Tg(Mt1-HGFSF)#Lmb/0 mice

increased cutaneous melanoma incidence ( J:111992 )

• untreated mice develop single, rapidly growing, spontaneous skin melanomas starting at ~30-40 weeks of age; ~20% of these mice have to be sacrificed by 1 year of age, with primary melanomas >10 mm in diameter

increased metastatic potential ( J:111992 )

• DMBA/TPA-treated mice show locoregional metastatic growth of melanoma cells in the draining lymph nodes as well as numerous melanoma micrometastases in lung tissue

• in lymph nodes of DMBA/TPA-treated mice, melanoma cells are mostly spindle-shaped cells with little/no melanin that eventually disrupt lymph node architecture and displace lymphoid cells; however, heavily pigmented epitheloid melanoma cells are also observed

• in DMBA/TPA-treated mice, the average number of lung metastases is significantly higher than that in DMBA/TPA-treated Cdk4^tm1.1Bbd/Cdk4⁺ Tg(Mt1-HGFSF)#Lmb/0 mice

• untreated mice with large spontaneous primary melanomas arising in skin also show locoregional metastases in adjacent draining lymph nodes as well as distal micrometastases in the lungs

increased tumor growth/size ( J:111992 )

• all DMBA/TPA-treated mice develop rapidly growing skin melanomas reaching >10 mm in diameter at 12 weeks of age

• few mitoses and a low % of Ki67 staining are noted in spindle-shaped melanoma cells near the invasion front, indicating proliferative activity of melanoma cells

increased skin tumor incidence ( J:111992 )

• at 30 weeks of age, untreated mice exhibit a similar number of melanocytic nevi in skin as untreated Tg(Mt1-HGFSF)#Lmb/0 mice

increased cutaneous melanoma incidence ( J:111992 )

• untreated mice develop single, rapidly growing, spontaneous skin melanomas starting at ~30-40 weeks of age; ~20% of these mice have to be sacrificed by 1 year of age, with primary melanomas >10 mm in diameter

abnormal axillary lymph node morphology ( J:111992 )

• at sacrifice, DMBA/TPA-treated mice show heavily pigmented axillary lymph nodes

enlarged axillary lymph nodes ( J:111992 )

• at sacrifice, DMBA/TPA-treated mice show enlarged axillary lymph nodes due to growth of melanoma cells

abnormal inguinal lymph node morphology ( J:111992 )

• at sacrifice, DMBA/TPA-treated mice show heavily pigmented inguinal lymph nodes

enlarged inguinal lymph nodes ( J:111992 )

• at sacrifice, DMBA/TPA-treated mice show enlarged inguinal lymph nodes due to growth of melanoma cells