Details

Autor(en) / Beteiligte

• Saha, Shekhar
• Dey, Sumit K.
• Das, Provas
• Jana, Siddhartha S.

Titel

Increased expression of nonmuscle myosin IIs is associated with 3MC‐induced mouse tumor

Ist Teil von

• The FEBS journal, 2011-11, Vol.278 (21), p.4025-4034

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Administration of the chemical carcinogen, 3‐methylcholanthrene (3MC), in the hind leg induces the progressive formation of tumors in mice within 110 days. Previous reports suggest that transformation of muscle cells to atypical cells is one of the causes of tumor formation. Molecular events that lead to transformation of normal cells to atypical cells are not well understood. Here, we investigate the effect of 3MC on the expression of nonmuscle myosin IIs (NM IIs) which are known to be involved in cell migration, division and adhesion. Mass spectroscopy analysis reveals that tumor tissue contains 64.5% NM II‐A, 34% II‐B and only 1.5% II‐C of total NM IIs, whereas these three isoforms of NM IIs are undetectable by mass spectroscopy in normal tissue associated with the tumor (NTAT) from the hind leg. Quantification of heavy chain mRNAs of NM II suggests that tumor tissue contains 25.7‐fold and 19.03‐fold more of NM II‐A and II‐B, respectively, compared with NTAT. Unlike NM II‐B, which is detected only after tumor formation, II‐A is detectable as early as day 7 after a second dose of 3MC. Immunofluorescence confocal microscopy reveals that fibroblast cells which are sparsely distributed in normal tissue are densely populated but of atypical shape in the tumor. These findings suggest that transformation of fibroblasts or non‐fibroblast cells to atypical, cancerous cells is associated with increased levels of NM II‐A and NM II‐B expression in the 3MC‐induced tumor mouse model. 3MC‐induced transformation is further demonstrated in C2C12 myotubes. Nonmuscle myosin IIs (NM IIs) are known to be involved in cell migration, division and adhesion. We report that expression of NM IIs is increased in 3‐methylcholanthrene (3MC) induced mouse tumor. Treatment of 3MC initiates dedifferentiation of C2C12‐myotube in our in vitro study. Dedifferentiation of muscle fibers along with fibroblast transformation could be cellular pathways for 3MC induced tumor formation in mice