Biology of the protein kinase C family

O’Brian, Catherine A.; Ward, Nancy E.

doi:10.1007/bf00047337

Cited by 115 publications

(63 citation statements)

References 106 publications

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“…PKC activation has been demonstrated as a controlling factor in the reabsorbtion activity exhibited by osteoclasts, a non-transformed cell type, responsible for bone remodeling (Moonga et al, 1996). PKC activity is also implicated in certain breast cancers where expression is higher in tumors compared with normal tissue (O'Brian and Ward, 1989).…”

Section: Introductionmentioning

confidence: 99%

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

et al. 1999

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Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (ECM). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) m, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We con®rmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates with cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.

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Section: Introductionmentioning

confidence: 99%

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

et al. 1999

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“…an altered cell membrane composition and changes in the expression and actixity of protein kinase C (PKC) isoenzymes (Endicott andLina. 1989: O'Brian andWard. 1989).…”

mentioning

confidence: 99%

Inhibition of protein kinase C-α isoform enhances the P-glycoprotein expression and the survival of LoVo human colon adenocarcinoma cells to doxorubicin exposure

Porta

Dolfini²,

Comolli³

1998

Br J Cancer

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Summary The aim of the present paper was to analyse the effect of long-term inhibitory treatment, for at least 7 days, of individual protein kinase C (PKC) isoforms on the survival of LoVo human colon adenocarcinoma cells to doxorubicin exposure. The treatment for 2 h, after plating the cells, and after 3 days with 1 gM Go6976, a specific inhibitor of protein kinase C (PKC)-a and -i1 isoforms, induced on day 7 in LoVo cell lines (WT) a significant increased survival when these cells were exposed to increasing doxorubicin concentrations. In contrast. resistant LoVo cells (DX) did not show significant changes in the survival to doxorubicin exposure when incubated with the inhibitor of the same specific PKC isoforms. In addition, G66976 reduced the PKC-a activity (the main calcium-dependent PKC isoforms expressed) in both cell lines with contemporary increased expression. Under such conditions. an increased nuclear activity and an increased P-glycoprotein expression occurred only in WT-treated cells with respect to untreated cells. Taken together, our data indicate a specific relationship between PKC-a inhibition, the increased nuclear PKC-a activity as well as the increased expression of P-glycoprotein. possibly causing the acquisition of a resistant phenotype in WT LoVo cells.

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“…Expression of PKC isotypes in tumours varies (Guillem et al 1987: O'Brian and Ward. 1989: Barr et al 1991: Couldwell et al 1991.…”

Section: Resultsmentioning

confidence: 99%

“…and are a common pathw ay in the regulation of cell growth by oncoproteins. PKC lex els may be altered in tumour cells (Guillem et al 1987: O'Brian and Ward. 1989: Barr et al 1991: Couldwell et al 1991.…”

mentioning

confidence: 99%

A phase II study of bryostatin 1 in metastatic malignant melanoma

Propper

Macaulay²,

O’Byrne³

et al. 1998

Br J Cancer

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Summary Bryostatin 1 is a protein kinase C partial agonist which has both antineoplastic and immune-stimulatory properties, including the induction of cytokine release and expansion of tumour-specific lymphocyte populations. In phase studies, tumour responses have been observed in patients with malignant melanoma, lymphoma and ovarian carcinoma. The dose-limiting toxicity is myalgia. Sixteen patients (age 35-76 years, median 57 years) with malignant melanoma were treated. All had received prior chemotherapy. In each cycle of treatment, patients received bryostatin 25 gg m-2 weekly for three courses followed by a rest week. The drug was given in PET diluent (10 gg bryostatin ml-of 60% polyethylene glycol, 30% ethanol, 10°h Tween 80) and infused in normal saline over 1 h. The principal toxicities were myalgia (grade 2, eight patients and grade 3. six patients) and grade 2 phlebitis (four patients), fatigue (three patients) and vomiting (one patient). Of 15 patients evaluable for tumour response, 14 developed progressive disease. One patient developed stable disease for 9 months after bryostatin treatment. In conclusion, single-agent bryostatin appears ineffective in the treatment of metastatic melanoma in patients previously treated with chemotherapy. It should. however, be investigated further in previously untreated patients.

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Biology of the protein kinase C family

Cited by 115 publications

References 106 publications

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

Inhibition of protein kinase C-α isoform enhances the P-glycoprotein expression and the survival of LoVo human colon adenocarcinoma cells to doxorubicin exposure

A phase II study of bryostatin 1 in metastatic malignant melanoma

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