Gene: maps to 12q13. Chromosome 12 contains several genes for type II keratins, including keratin 8, and also the gene for
keratin 18, the type I keratin that is coexpressed with keratin 8. This location of both members of a keratin pair on a single chromosome is unique among keratin genes; it is consistent with the hypothesis that keratins 8 and 18 may be closer to an ancestral gene than the keratins of more highly differentiated epithelia (Waseem A. et al., 1990).
mRNA: size: kb.
Protein:
Intermediate filaments (IFs) are a structurally related family of cellular proteins that appear to be intimately involved with the cytoskeleton. The common structural motif shared by all IFs is a central alpha-helical 'rod domain' flanked by variable N- and C-terminal domains. The rod domain, the canonical feature of IFs, has been highly conserved during evolution. The variable terminals, however, have allowed the known IFs to be classified into 6 distinct types by virtue of their differing amino acid sequences (Steinert P.M. and Roop D.R., 1988). Keratins compose types I and II; intermediate filaments desmin, vimentin, GFAP, and peripherin, type III; neurofilaments, type IV, and nuclear lamins, type V. Nestin has been classed as type VI. The acidic keratins are coded by genes KRT9 to KRT19. These genes are located on human chromosome 17, except for KRT18 which may be located on human chromosome 12. The basic keratins are coded by genes KRT1 to KRT8, which are located on human chromosome 12.
Cell lines:
- KRT8 binds plasminogen and
tissue-type plasminogen activator (t-PA) and accelerates plasminogen activation on cancer cell surfaces. The plasminogen-binding site is located at the C-terminus of KRT8. It was demonstrated that KRT8 may promote plasminogen activation by
t-PA only when present in an oligomerized state.
Cytokeratin 18 may participate in the oligomer, together with KRT8, based on its ability to bind
t-PA (Kralovich K.R. et al., 1998).
- 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, 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:
- Keratin 8 was found non-suitable for RT-PCR detection of submicroscopic lymph node metastases in breast cancer, as its transcript was also detected in the great majority of control (from non-cancer patients) lymph nodes tested (Merrie AEH et al., 1999).
Kralovich K.R. et al. (1998) Characterization of the binding sites for plasminogen and tissue-type plasminogen activator in
cytokeratin 8 and
cytokeratin 18. J. Protein Chem. 17, 845-854.
Merrie AEH et al. (1999) Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer. Br. J. Cancer 80, 2019-2024.
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.
Steinert P.M. and Roop D.R. (1988) Molecular and cellular biology of intermediate filaments. Ann. Rev. Biochem. 57, 593-625.
Waseem A. et al. (1990) Embryonic simple epithelial keratins 8 and 18: chromosomal location emphasizes difference from other keratin pairs. New Biologist 2, 464-478.
Yamamoto R. et al. (1990) Cloning and sequence of cDNA for human placental cytokeratin 8: regulation of the mRNA in trophoblastic cells by cAMP. Molec. Endocr. 4, 370-374.
