Is Fimbrin Involved in Cancer

The potential of fimbrin to modulate cell behaviour is obviously quite considerable. There are references in the literature since the early 1980s that fimbrin expression increases with cell transformation, especially in fibroblast cells. However, little incisive investigation seems to have been carried out. More recent investigations have pursued the worthwhile aim of establishing a role for fimbrin in neoplastic transformation and tumour progression. The expression of L-fimbrin has been...

Relationship Between S100A4 S100A4v and nm23 Expression to Nodal Spread of Breast Cancer

Gene Expressed Relationship to Nodal Spread3 a +, statistically significant relationship (p < .05) ++, strong relationship (p < .01). b The expression of S100A4v (the splice variant form) alone did not relate to nodal spread however, tumours that express neither S100A4 nor S100A4v do not tend to spread to the regional lymph nodes. Only 27 of carcinomas expressing neither h-mts1 nor h-mts1v showed metastatic spread to the lymph nodes 57 (4 7) of carcinomas in which only the variant isoform...

Calreticulin And Its Functional Diversity

Structure and Molecular Features of Calreticulin Two types of CBPs are associated with the endoplasmic reticulum (ER), namely reticulocalbin (an EF-hand CBP whose localisation and function are discussed in Chapter 12 and calreticulin). Calreticulin is a non-EF-hand CBP that is ubiquitously associated with the ER of a variety of tissues. It is regarded as the nonmuscle equivalent of calsequestrin, which is associated with the sarcoplasmic reticulum (SR). Calreticulin, which was identified as a...

Calmodulin in Neoplasia

An enhancement of CaM has been recognised as a feature of cell transformation and of malignant cells. CaM levels of human lung cancer cells are higher than that of benign tumours of the lung or normal lung tissue (Liu G.X. et al. 1996). These authors also describe a correlation between tumour grade and TNM stage and levels of CaM. However, Edelman et al. (1994) have described a CaM-like protein that is apparently restricted to epithelial cells. This CaM-like protein was identical in size and...

Calcineurin In Immunosuppression

Calcineurin plays a key role in immunosuppression. There has been an unequivocal demonstration over the past few years that the drugs cyclosporin A, FK506, and rapamycin achieve immune suppression by inhibiting the function of calcineurin. That calcineurin was the target of some of these immunosuppressants was established some years ago. O'Keefe et al. (1992) transfected the catalytic calcineurin A into cells and showed that this raises the IC50 inhibitory concentration of cyclosporin and...

Osteonectin Expression In Cancer Development And Progression

Osteonectin seems to be able to influence most of the biological properties of the cell that are highly relevant in the context of cancer development, growth, and dissemination. The most obvious reasons for this are that osteonectin is able to initiate changes in the ECM, cell adhesion and spreading, and also in the cytoskel-eton. It has been found to influence cell proliferation, and apparently, it can regulate vascularisation. The elucidation of these properties has inevitably led to the...

The Sarcoplasmic Endoplasmic Reticulum Ca2ATPase Pump

SERCA is one of the modes that controls the homeostasis of intracellular calcium. SERCA2 transports Ca2+ into the lumen of the reticulum by an ATP-dependent mechanism. By virtue of this ability, SERCA2 plays an important part in normal physiological function such as the contraction and relaxation cycle of cardiac muscle, as well as in the pathogenesis of certain diseases. In addition, the correct localisation of the SERCA protein in the ER is of the utmost importance. As stated above, the...

Osteocalcin in Cell Proliferation and Differentiation

The osteocalcin gene is expressed in consonance with the inhibition of cell proliferation and the onset of cell differentiation and ECM mineralisation (Y.P. Li et al. 1995). VD3, as discussed above, induces osteocalcin expression, but on the other hand, it inhibits cell proliferation, apparently with the mediation of cdk inhibitors. M.J. Campbell et al. (1997) synthesised a number of VD3 analogues and demonstrated that these were capable of inhibiting proliferation of the prostate cancer cell...

Deregulation Of Inositol 145trisphosphate Pathway And Its Consequences

It is hardly surprising that interference with signal transduction pathways and their deregulation should have serious consequences for biological responses in developmental systems as well as in pathogenesis. Ecdysone, a steroid hormone, regulates a variety of developmental processes and metamorphosis in insects. It also influences neuronal responses, apoptosis, and histiolysis in a variety of larval tissues, binds to nuclear receptors, which show tissue- and stage-specific expression...

S100A4 in Human Breast Cancer

Pedrocchi et al. (1994) first described the importance of S100A4 in breast cancer cell lines. Recently, Albertazzi et al. (1998b) have published a detailed study of S100A4 expression, not only in relation to the degree of aggressiveness of the disease, but also as to how it relates to other clinical markers such as the status of oestrogen and progesterone receptors and the degree of tumour differentiation. Albertazzi et al. (1998b) also employed another marker, nm23-H1. nm23 is a putative...

Calmodulin and Cell Proliferation

As stated earlier, among the targets of CaM are the cytoskeletal proteins MAP-2 and the tau protein. The conclusion is inescapable, therefore, that CaM might be involved in cytoskeletal reorganisation. Both cell proliferation and cell motility have been regarded as the natural foci of CaM involvement. CaM seems to be actively associated with cell proliferation, as amply demonstrated by several investigators. Indeed, it is regarded as an essential ingredient of cell proliferation and the...

Calbindin Expression And The Metastatic Phenotype

The ability of steroids to influence the expression of calbindins has led to investigations aimed at examining their potential involvement in the development and growth of tumours, their progression, and prognosis. Watanabe et al. (1994) investigated CBD levels of lung cancers. The levels of CBD were low in normal lung tissue, but its expression was higher in lung cancers, with SCLC tissue expressing greater amounts than non-SCLC (NSCLC). Furthermore, CBD levels correlated with progression of...

Caspasemediated Apoptosis And Cell Growth Inhibition In Tumour Expansion

The relevance of caspase-mediated apoptosis in tumour development has been emphasised recently by the finding that enhanced expression of caspase-2 leads to a reversion of ras-induced transformation in NIH3T3 cells (Hiwasa and Nakagawara, 1998). Hiwasa and Nakagawara (1998) transfected caspase cDNAs into c-Ha-ras-transformed cells. Enhanced expression of caspase-2 alone, but not caspases 1 and 2 together, resulted in a reduction in the ability of the transfected cell to grow in soft agar. This...

Pten Phosphatase In The Regulation Of Lipid Signalling

Phosphoinositide-3 kinase (PI3K) is responsible for the phosphorylation and generation of PIP2 and PIP3. This phosphorylation is antagonised by a phosphatase that is encoded by the gene called PTEN MMAC1 TEP1 located on chromosome 10q23. The phosphatase, referred to here as PTEN, shows sequence homology to tensin (Steck et al. 1997). The phosphatase activity is essential for the normal functioning of PTEN (Tamura et al. 1999b). PTEN regulates the levels of the phosphoinositol phosphates by...

Osteocalcin In Bone Metabolism And Osteotropism Of Cancer

Osteocalcin is a noncollagenous protein. It is the most abundant matrix protein of bone and dentine (Price, 1992). It is regarded as a marker of bone turnover and metabolism, where bone resorption and formation are coupled. Osteocalcin is syn-thesised exclusively by osteoblasts and secreted into the extracellular matrix (ECM) during bone mineralisation. It is released also during osteoclastic degradation. Therefore, it is considered to be a marker of bone formation when formation and resorption...

S100A4 Expression and Metastatic Potential of Cancers

The considerable influence that S100A4 exerts over cell adhesion, motility, and cell proliferation has prompted the investigation of the possible relevance of its expression in tumour development and their progression to the metastatic state. S100A4 is found in a variety of normal tissues of both murine and human origin (Grigorian et al. 1994 Gibbs et al. 1995). It occurs in normal adult rat tissues such as smooth muscle, brown adipose tissue, and the liver. Other tissues, e.g., normal breast...

Calpains In Myelodegenerative Diseases

During early stages of brain development, calpains show a pattern of expression that is compatible with the view that they are mainly associated with the formation of the myelin sheath. Subsequent to this, they are found in the cytosol rather than in the myelin sheath. Myelin basic protein MBP and myelin-associated glycoprotein are substrates of calpain. Banik et al. 1994 have shown that component I of human MBP is more susceptible to proteolysis by calpain than components II and III. They have...

The Fimbrin Family Of Actinbinding Proteins

Fimbrins are EF-hand calcium-binding proteins that actively participate in binding to and bundling of actin. In actin filaments, one molecule of fimbrin might bind eight actin monomers under optimal conditions Namba et al. 1992 . Fimbrins are highly conserved in evolution, with regard to both their structure and function. Fimbrin from diverse origins, e.g., from Dictyostelium discoideum to humans, share structural and biochemical properties. Fimbrin-like proteins have also been isolated from...

Camkiv

FIGURE 8 Phosphorylation of the transcription factors CREB cyclic AMP response element binding protein and ATF in the negative and positive regulation of genetic activity. The Ca2 CaM-activated protein kinases CAMKIV and CAMKII phosphorylate specific positive and negative regulatory serine residues of the transcription factors, which therefore differentially transactivate the responsive genes. targeted and conveyed to specific subcellular compartments for eliciting cellular responses. This...

The Gelsolin Family Of Calciumbinding Proteins

Actin-binding proteins constitute a large family of proteins that actively participate in actin bundling, nucleation, actin capping, and severing. Gelsolin, severin, and villin are three important proteins of the gelsolin family of actin-binding proteins that will be discussed here, for they possess the remarkable property of rapidly reorganising the cytoskeleton and also rapidly modulating, in a Ca2 -dependent manner, cell shape, substrate adhesion, and cell locomotion. Gelsolin in Severing...

Osteotropism Of Metastatic Dissemination

Metastatic spread of cancer is a nonrandom process. The perceived organ specificity of metastasis can be attributed to a variety of factors intrinsic to the cancer cell as well as to the target organs see Sherbet, 1982 for review . Metastatic spread to the bone is a common occurrence in certain forms of cancer. It has been argued often that bone metastases can activate the processes of bone metabolism. For that reason osteocalcin has been regarded as a potential surrogate method for detecting...

Calpains In Cancer Growth And Progression

Calpain is significantly involved, as discussed above, in a number of physiological processes that are integral features of the development and progression of cancer. We have seen that the suppressor phosphoprotein p53, which is closely linked with the control of cell cycle progression, is degraded by calpain. Mutations of p53 gene are a common event in tumorigenesis, and these lead to the abrogation of normal checkpoint control function exerted by wild-type p53. We have noted also that calpain...

Calcineurin In Cell Proliferation And Adhesionrelated Phenomena

Calcineurin has been implicated in a number of physiological events, such as cell proliferation, cell death, and signal transduction, and in immunosuppression. It also has been implicated in certain functions of the nervous system, e.g., in neurotransmission. The discussion here will be restricted mainly to areas pertinent to the biological behaviour of cancers, although some reference will be made to Alzheimer's disease, in which cytoskeletal abnormalities occur prominently. The regulation of...

The Role Of Thymosin Family Actinbinding Proteins In Actin Dynamics

The beta thymosins constitute an important family of actin-binding proteins, which are recognised as major participants in the regulation of actin dynamics. Among its members are TP4, TP 10, and TP 15, which are the most intensively investigated forms of thymosin. TP4 is a 4.5-kDa protein consisting of 43 amino acid residues. TP 14 is another protein isolated from the sea urchin, that has 40 amino acid residues and a molecular size of 4.53 kDa and bears a high degree of sequence homology to TP4...

Regulation Of Physiological Events By Proteolytic Function

Calpains are not wide-spectrum proteases. Importantly, the limited number of substrates that they cleave are involved with the activation of specific cellular systems. Notable among their substrates are PKC-y, the actin-binding proteins, a-fodrin and the homologous a- and p-spectrin, and growth factor receptor proteins Lofvenberg and Backman, 1999 Saido et al. 1994 Croall and De Martino, 1991 Martin et al. 1995 . It is to be expected that calpains would be involved in physiological events...

Recoverin and Cancer Associated Retinopathy in Small Cell Lung Cancer

A degeneration of the retina is infrequently associated as a paraneoplastic condition with some forms of cancer. This condition, often described as cancer-associated retinopathy CAR , is an autoimmune syndrome involving the degeneration of the photoreceptor cells of the eyes. Injection of RCN had previously been shown to induce degeneration of photoreceptor cells of the eyes of Lewis rats, and this was correlated with high titres of RCN antibodies in the circulation Adamus et al. 1994 . There...

Calreticulin in Neoplasia

Although the above discussion indicates a significant involvement of calreticulin in cell adhesion and possibly also in cell proliferation, only a few studies have dealt with its occurrence in tumours. Of the multiple functions attributed to calreticulin, its perceived effects on cell proliferation are the most relevant in relation to cancer. Calreticulin is one of several peptides of human breast cancers studied by Franzen et al. 1997 . They state that it is expressed at higher levels in...

Annexins

Several non-EF-hand CBPs have been identified and sequenced. Of these, annexins have been studied extensively. Annexins form a family of structurally related and highly conserved proteins that bind phospholipids in a Ca2 -dependent manner. Several annexins have been identified and some of these have been well characterised, e.g., annexins I, IV, V, and XII. A 40-kDa annexin, distinct from annexin XII, has been reported from Hydra vulgaris Schlaepfer et al. 1992a . Although basically annexins...

The Protein Kinase C Pathway

Pkc Pathway Calcium

Growth factors and hormones are known to increase the intracellular Ca2 Ca2 d , either by releasing Ca2 from intracellular stores or by promoting Ca2 influx. Ca2 controls several biological functions, mainly by mediating the phosphorylation of cellular effector proteins. Calcium-binding proteins transduce the calcium signals to specific subcellular compartments. The generation of second messengers such as IP3, 1,2-diacylglycerol DAG , and cyclic 3',4'-adenosine monophosphate cAMP is a major...