Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo.
Malignant melanoma (MM) is characterized by aggressive metastasis and high mortality rate. Microtubule-associated proteins 2 (MAP2) is expressed abundantly in majority of melanocytic nevi and primary melanomas, but absent in metastatic melanomas. To determine whether MAP2 correlates with tumor progression of MM, we investigated the effects of MAP2 inhibition on the biological behaviour of metastatic melanoma in vitro and in vivo. Our results demonstrated that adenovirus-mediated MAP2 induced apoptotic cell death and cell cycle arrest in metastatic human and mouse melanoma cell lines in vitro, and substantially inhibited the growth of melanomas in nude mice in vivo. In addition, intracellular expression of MAP2 was found to induce the morphologic alteration, suppress the migration and invasion and affect the assembly, stabilization and bundling of microtubules in melanoma cells. This is the first study that MAP2 expression significantly inhibits the growth of MM in vivo. Our results suggest that MAP2 may serve as a promising molecular target for therapy and chemoprevention of MM in humans.
Song
Zhiqi
Z
Department of Dermatology, No. 1 Hospital of China Medical University, Key Laboratory of Immunodermatology, Ministry of Health (China Medical University), Shenyang, China. szqdalian@yahoo.com
He
Chun-Di
CD
Sun
Changkai
C
Xu
Yanni
Y
Jin
Xin
X
Zhang
Yi
Y
Xiao
Ting
T
Wang
Yakun
Y
Lu
Ping
P
Jiang
Yi
Y
Wei
Huachen
H
Chen
Hong-Duo
HD
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape / Q000502:physiology; D022081:Cell Surface Extensions / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D014161:Transduction, Genetic
C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse