Vimentin

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Gene: the single-copy VIM gene maps to 10p13.
mRNA: size: 1.9-2 kb (Ferrari S. et al., 1986).
Protein: a component of the the intermediate filaments (cytoskeletal elements). Mice homozygous for a null mutation in the vimentin gene developed and reproduced without an obvious deviant phenotype. No compensatory expression of another intermediate filament could be demonstrated. Vimentin could play a significant role only in pathologic or unusual conditions (Colucci-Guyon E. et al., 1994).

Cell lines:
- By immunofluorescence, vimentin was found in the ER-alpha-negative, keratin-negative, E-cadherin-negative, in vitro highly invasive fibroblast-like MDA-MB-231, -435, -436, BT549, Hs578T, and MCF-7/Adr (doxorubicin resistant) breast cancer cell (BCC) lines. It was absent in the ER-alpha-positive, keratin-positive, E-cadherin-positive, ZO-1-positive, in vitro poorly invasive, and epithelioid BT483, MDA-MB-175 and -361, MCF-7, ZR-75-B, T-47D, and BT474 BCC lines (Sommers C.L. et al., 1994a).

- Comparison of vimentin-positive (V+) and vimentin-negative (V-) breast cancer cell lines revealed several potential areas of vimentin gene regulation. Analysis of the chromatin structure of the vimentin gene in V+ and V- breast cancer cells showed DNase I hypersensitive sites in the 5' promoter region in V+ cell lines and 3' to the start of transcription in V- cell lines. Promoter deletion and reporter gene analysis revealed the importance of two adjacent AP-1 sites separated by seven GC-rich nucleotides for vimentin expression in V+ breast cancer cells. Mutational analysis of these sequences showed that although both AP-1 sites could bind nuclear proteins from V+ cells in vitro, one AP-1 site was sufficient to drive transcription in CAT reporter gene assays. The GC-rich spacer region had a modulating function on the activity of the AP-1 sites. In addition, levels of c-jun mRNA were elevated in V+ versus V- cells (Sommers C.L. et al., 1994b).

- BCC lines that express vimentin appeared highly invasive in vitro and highly metastatic in nude mice in comparison with vimentin-negative cell lines (Pulyaeva H. et al., 1997).

- Overexpression of vimentin in MCF-7 BCC led to augmentation of motility and invasiveness in vitro. These activities could be transiently down-regulated by vimentin antisense oligonucleotides in vimentin-overexpressing MCF-7 clones and in MDA-MB-231 BCC (which constitutively co-express keratins and vimentin). Furthermore, in the vimentin-overexpressing MCF-7 transfectants exhibiting the highest percentage of vimentin-positive cells, their proliferative capacity, clonogenic potential, and tumorigenicity increased. However, the metastatic ability of the vimentin-overexpressing MCF-7 clones remained unchanged compared with MCF-7neo controls (Hendrix M.J. et al., 1997).

- The phenotypic characteristics of 2 tumor cell lines (BC-H1 and BC-K1) established from bone marrow of patients with breast cancer were studied by immunocytochemistry, flow cytometry, and RT-PCR. Both cell lines expressed E-cadherin, vimentin, cytokeratins (including component 18), alpha 5-, alpha V-, beta 1-, and beta 3- integrin subunits, ICAM-1, MCAM, LFA-3 (CD58), and CD44s (but not CD44v5, v6, v7/8). BC-H1 also expressed ErbB2 (not found in BC-K1), and MAGE-4 (but not MAGE-1, -2, -3/6, -12; BC-K1 was not tested). In both cell lines, the mesenchymal cytoskeleton protein vimentin was coexpressed with cytokeratins CK8/18 and CK8/19, indicating an epithelial to mesenchymal transition of these micrometastatic cells. The expressed molecules might be potential candidates for novel therapeutic targets (Putz E. et al., 1999).

Tumors:
- Expression of vimentin in human breast cancer is associated with markers of disease aggression such as high grade, low estrogen receptor status, and high Ki-67 growth fraction (Domagala W. et al., 1990 and 1990b).

- The expression of keratin and vimentin were measured in 54 archival, formalin-fixed, paraffin-embedded invasive breast cancers from postmenopausal women. Vimentin expression was inversely associated with keratin expression alone (P = 0.0089) and directly related to histological grade (P = 0.017), nuclear grade (P = 0.027), Ki67 growth fraction (P = 0.024), and epidermal growth factor receptor immunostaining (P = 0.019). The relative expression of keratin and vimentin in approximately similar amounts characterized tumors with the poorest prognosis, as compared with keratin-high/vimentin-negative or keratin-low/vimentin-positive tumors, suggesting that keratin and vimentin intermediate filament (IF) coexpression in breast cancer confers a more aggressive "interconverted" phenotype, expressing both epithelial and mesenchymal markers (Thomas P.A. et al., 1999).

Colucci-Guyon E. et al. (1994) Mice lacking vimentin develop and reproduce without an obvious deviant phenotype. Cell 79, 679-694.
Domagala W. et al. (1990) Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction. Am. J. Pathol. 136, 219-227.
Domagala W. et al. (1990b) Vimentin is preferentially expressed in high grade ductal and medullary, but not in lobular breast carcinomas. Am. J. Pathol. 137, 1059-1064.
Ferrari S. et al. (1986) Coding sequence and growth regulation of the human vimentin gene. Molec. Cell. Biol. 6, 3614-3620.
Ferrari S. et al. (1987) The gene encoding human vimentin is located on the short arm of chromosome 10. Am. J. Hum. Genet. 41, 616-626.
Hendrix M.J. et al. (1997) Experimental co-expression of vimentin and keratin intermediate filaments in human breast cancer cells results in phenotypic interconversion and increased invasive behavior. Am. J. Pathol. 150, 483-495.
Perreau J. et al. (1988) Nucleotide sequence of the human vimentin gene and regulation of its transcription in tissues and cultured cells. Gene 62, 7-16.
Pulyaeva H. et al. (1997) MT1-MMP correlates with MMP-2 activation potential seen after epithelial-to-mesenchymal transition in human breast carcinoma cells. Clin. Exp. Metastasis 15, 111-120.
Putz E. et al. (1999) Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241-248.
Sommers C.L. et al. (1994a) Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res. Treat. 31, 325-335.
Sommers C.L. et al. (1994b) Regulation of vimentin gene transcription in human breast cancer cell lines. Cell Growth Differ. 5, 839-846.
Thomas P.A. et al. (1999) Association between keratin and vimentin expression, malignant phenotype, and survival in postmenopausal breast cancer patients. Clin. Cancer Res. 5, 2698-2703.

Keratin 8 (KRT8), keratin 18 (KRT18), keratin 19 (KRT19), intermediate filaments