Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation.

Mellström, Karin; Bjelfman, C; Hammerling, Ulf; Påhlman, Sven

doi:10.1128/mcb.7.12.4178

Cited by 60 publications

(36 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylation of y-enolase led to partly inactivation of the enzyme, accompanied by an increase of the total amount of the enzyme (Eigenbrodt et al, 1983). Moreover c-src expression in neuroblastoma-and SCLC-cell lines correlated with neuroendocrine differentiation (Mellstrom et al, 1987) and c-src is connected to neurogenesis and neuronal differentiation (Brickel et al, 1991), as is the switch from a to y-enolase (Schmechel et al, 1980). In this connection it is very interesting that Wevers et al (1988) found in cerebrospinal fluid but not in serum from healthy individuals that 50% of NSE-ag had no enzyme activity.…”

Section: Discussionmentioning

confidence: 96%

Distinction of two different classes of small-cell lung cancer cell lines by enzymatically inactive neuron-specific enolase

Splinter

Verkoelen²,

Vlastuin³

et al. 1992

Br J Cancer

View full text Add to dashboard Cite

Summary Neuron specific enolase (NSE) is widely used as a neuro-endoctrine marker. However the presence of NSE in many non-neuroendocrine tissues has raised questions on the specificity of NSE. We have investigated NSE immunoreactivity (NSA-ag), y-enolase activity and total enolase activity in small cell lung cancer (SCLC) (Bepler et al., 1987;Carney et al., 1985;Gazdar et al., 1985;Bepler et al., 1989a;Broers et al., 1985;Moody et al., 1985;Broers et al., 1988 NSE is widely used as a neuroendocrine marker. NSEimmuno reactivity is not only seen in neurons, but also in neuroendocrine cells present in endocrine glands and in the diffuse neuroendocrine systems of the lung, intestine, thymus and skin. NSE has been demonstrated in tumours, thought to arise from the neuroendocrine cell system, such as SCLC, neuroblastoma, carcinoid, pancreatic islet cell tumours and medullary thyroid carcinoma (Schmechel et al., 1978;Tapia et al., 1981;Wick et al., 1983). NSE is also present in erythrocytes, lymphocytes and platelets (Marangos et al., 1980b;Hullin et al., 1980) and in malignant lymphomas, testicular cancer, hypernephroma and non-small cell lung cancer (Takashi et al., 1989;Ariyoshi et al., 1983;Kuzmits et al., 1987;Pinto et al., 1989;Oka et al., 1989;Niehans et al. 1988). Such observations question the correlation between NSE and the neuroendocrine cell system (Schmechel, 1985 SCLC-cell linesThe SCLC-cell lines were generously provided by the

show abstract

Section: Discussionmentioning

confidence: 96%

Distinction of two different classes of small-cell lung cancer cell lines by enzymatically inactive neuron-specific enolase

Splinter

Verkoelen²,

Vlastuin³

et al. 1992

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…In addition, primary neurons induced to differentiate in culture, display increased expression of pp60"c with elevated kinase activity (22). A correlation of the level of pp60csrc expression with differentiation events in this tissue is further strengthened by the observation of similar biochemical events in human tumors of neuronal and neuroendocrine origin (16,17,23). In contrast, human tumor cells of neuroectodermal origin, which do express neural characteristics, were found to have moderate to low levels of pp6Oc-src kinase activity ( 17).…”

Section: Introductionmentioning

confidence: 88%

“…These results suggest a role for the src protooncogene in colon differentiation pathways of colon mucosa. The involvement of pp6Oc-src in differentiation pathways of the nervous system has been established (18,19,20) and is maintained in neoplastic lesions, where elevated src kinase activity was observed in human tumors of neuronal and neuroendocrine origin (16,17,23) but not in tumor cells of neuroectodermal origin (17), which do not express neural characteristics. In contrast, activation ofthe pp6O>src protein kinase is found as an early event in colonic polyps (3) displaying a gradation in activity associated with progression and maintained in 70% of colon carcinomas studied (2,24).…”

Section: Discussionmentioning

confidence: 99%

Differential pp60c-src activity in well and poorly differentiated human colon carcinomas and cell lines.

Weber¹,

Steele²,

Summerhayes³

1992

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The The c-src+ gene product has never been detected in cultures of nonneuronal cells or in nonneural tissues (3,5; J. Bolen and N. Rosen, personal communication). Several lines of evidence suggest that pp6oc-sr,+ is a neuron-specific protein: (i) cultured rat neuronal cells contain high levels of the structurally distinct form of the c-src gene product (5); (ii) pp60CxrC is induced upon differentiation of teratocarcinoma cells into neuronlike cells (36); (iii) several neuroblastoma cell lines express the neural-specific c-src+ protein (3,39,53); and (iv) analyses of pp60c-srs in mutant mice strains that display a progressive loss of specific classes of cerebellar neuronal cells show a strong correlation between the degeneration of the cerebellar neuronal cells and the disappearance of the c-src+ protein (6).The c-src+ gene product extracted from neurons displays a higher specific activity in immunocomplex protein kinase assays than does pp60c-src from astrocytes or fibroblasts (5,8,9). There are at least two major structural differences between the c-src proteins produced in neuronal cells and nonneuronal cells that could contribute to this enhanced activity: (i) the hexapeptide insert (32, 37) and (ii) a novel site(s) of serine phosphorylation within the amino-terminal 16,000 daltons (Da) of the c-src+ protein (4,9).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Biological and biochemical properties of the c-src+ gene product overexpressed in chicken embryo fibroblasts.

Levy¹,

Brugge²

1989

Mol. Cell. Biol.

View full text Add to dashboard Cite

The c-src protein isolated from neuronal cells (pp6Oc-src) displays a higher level of protein kinase activity than does pp6O-src from nonneural tissues. There are two structural alterations present in the amino-terminal half of pp60`rC expressed in neurons which could contribute to the enhanced activity of this form of pp6Oc-src (i) a hexapeptide insert located at amino acid 114 of avian pp60c-src and (ii) a novel site(s) of serine phosphorylation. We characterized pp6oc-src+ expressed in a nonneuronal cell type to identify factors that regulate the activity of the c-src+ protein and the importance of the neuronal environment on this regulation.The c-src+ protein overexpressed in chicken embryo fibroblasts (CEFs) displayed higher kinase activity than did pp60c-src. The major sites of phosphorylation of the c-src+ protein were Ser-17 and Tyr-527. The unique site(s) of serine phosphorylation originally identified in pp60c-src expressed in neurons was not detected in the c-src+ protein overexpressed in CEFs. Therefore, the hexapeptide insert is sufficient to cause an elevation in the tyrosine protein kinase activity of pp6Ocsrc+. Our data also indicate that CEFs infected with the Rous sarcoma virus (RSV)c-src+ display phenotypic changes that distinguish them from cultures producing pp60csrc and that pp6oc-src -expressing cells are better able to grow in an anchorage-independent manner. The level of total cellular tyrosine phosphorylation in RSVc-src+-infected cultures was moderately higher than the level observed in cultures infected with RSVc-src. This level was not as pronounced as that observed in cells infected with RSVv-src or oncogenic variants of RSVc-src. Thus, pp60csrc could be considered a partially activated c-src variant protein much like other c-src proteins that contain mutations in the amino-terminal domain.The c-src gene has served as a model system in investigations of the function and importance of a large family of proto-oncogene products, the protein tyrosine kinases. High levels of the c-src protein (pp60c-src) have been identified in neural tissues (5,14,17,31,47,49), platelets (21), peripheral blood lymphocytes (21), monocytes (1, 18), and chromaffin cells (41). The majority of the c-src gene product expressed in neural tissues, however, is structurally distinct from the protein produced in nonneural tissues (4, 5) and is encoded by a uniquely processed c-src mRNA (4, 32, 37). Neuralspecific c-src cDNA clones isolated from both chicken brain (32) and mouse brain (37) cDNA libraries contain an 18-base-pair insertion located at the splice junction between exons 3 and 4 of the c-src gene. The additional six amino acids encoded by this miniexon are identical in avian and mammalian species, and this insertion is responsible for the altered electrophoretic mobility of the c-src protein in neuronal cells (designated pp6Oc-src ) (32, 37).The hexapeptide insert, located at amino acid 114 of avian pp60c-src (amino acid 117 of mammalian pp6OCs'C), lies outside the catalytic domain of pp6Ocsr', within a ...

show abstract

Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation.

Cited by 60 publications

References 45 publications

Distinction of two different classes of small-cell lung cancer cell lines by enzymatically inactive neuron-specific enolase

Distinction of two different classes of small-cell lung cancer cell lines by enzymatically inactive neuron-specific enolase

Differential pp60c-src activity in well and poorly differentiated human colon carcinomas and cell lines.

Biological and biochemical properties of the c-src+ gene product overexpressed in chicken embryo fibroblasts.

Contact Info

Product

Resources

About