Suppression of the transformed phenotype of breast cancer by tropomyosin-1.
Changes in the expression of microfilament-associated proteins, such as tropomyosins (TMs), are commonly found in malignantly transformed cells. Previous work from this laboratory has shown that tropomyosin-1 (TM1) expression is consistently abolished in human breast carcinoma cell lines, suggesting that the loss of TM1 could be a common biochemical event in the transformation of mammary epithelium. To investigate whether changes in TM1 expression are causally linked to mammary carcinogenesis, we have tested the hypothesis that TM1 is a tumor suppressor of breast cancer. MCF-7 cells, which lack TM1, were utilized as a model of human breast cancer and transduced to reexpress TM1 protein. Restoration of TM1 expression in MCF-7 cells (MCF-7/T cells) resulted in a slower growth rate, but cells remained sensitive to growth control by estrogen. TM1 expression in MCF-7 cells resulted in the emergence of TM-containing microfilaments. More significantly, MCF-7/T cells failed to grow under anchorage-independent conditions. TM1 reexpression alters the interaction of the E-cadherin-catenin complex with the cytoskeleton, indicating that TM1-induced cytoskeleton could play a significant role in suppression of the malignant phenotype. Taken together with our previous work on transformed murine fibroblasts, the results presented in this communication indicate that in nonmuscle cells TM1 functions as a suppressor of transformation.
Mahadev
Kalyankar
K
Department of General Surgery and Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Raval
Gira
G
Bharadwaj
Shantaram
S
Willingham
Mark C
MC
Lange
Ethan M
EM
Vonderhaar
Barbara
B
Salomon
David
D
Prasad
G L
GL
D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D029721:Drosophila Proteins; D006801:Humans; D007700:Kinetics; D010641:Phenotype; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014161:Transduction, Genetic; D014335:Tropomyosin / Q000502:physiology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D012334:RNA, Neoplasm; C490775:TPM1 protein, human; C097163:Tm2 protein, Drosophila; D014335:Tropomyosin; D025521:Tumor Suppressor Proteins