High-molecular-weight tropomyosins localize to the contractile rings of dividing CNS cells but are absent from malignant pediatric and adult CNS tumors.
Tropomyosin has been implicated in the control of actin filament dynamics during cell migration, morphogenesis, and cytokinesis. In order to gain insight into the role of tropomyosins in cell division, we examined their expression in developing and neoplastic brain tissue. We found that the high-molecular-weight tropomyosins are downregulated at birth, which correlates with glial cell differentiation and withdrawal of most cells from the cell cycle. Expression of these isoforms was restricted to proliferative areas in the embryonic brain and was absent from the adult, where the majority of cells are quiescent. However, they were induced under conditions where glial cells became proliferative in response to injury. During cytokinesis, these tropomyosin isoforms were associated with the contractile ring. We also investigated tropomyosin expression in neoplastic CNS tissues. Low-grade astrocytic tumors expressed high-molecular-weight tropomyosins, while highly malignant CNS tumors of diverse origin did not (P </= 0.001). Furthermore, high-molecular-weight tropomyosins were absent from the contractile ring in highly malignant astrocytoma cells. Our findings suggest a role for high-molecular-weight tropomyosins in astrocyte cytokinesis, although highly malignant CNS tumors are still able to undergo cell division in their absence. Additionally, the correlation between high-molecular-weight tropomyosin expression and tumor grade suggests that tropomyosins are potentially useful as indicators of CNS tumor grade.
Hughes
Julie A I
JA
Oncology Research Unit, Children's Hospital at Westmead, Australia.
Cooke-Yarborough
Claire M
CM
Chadwick
Nigel C
NC
Schevzov
Galina
G
Arbuckle
Susan M
SM
Gunning
Peter
P
Weinberger
Ron P
RP
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003285:Contractile Proteins / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D051379:Mice; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis; D014335:Tropomyosin / Q000032:analysis / Q000096:biosynthesis*
D003285:Contractile Proteins; D020033:Protein Isoforms; D014335:Tropomyosin