HER-2/neu, c-Myc and cyclin-A in human breast cancer

Tommasi, Stella; Giannella, C.; Mangia, A.; Primavera, A. T.; Paradiso, A; Schittulli, F.

doi:10.3892/ijo.9.1.111

Cited by 2 publications

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“…Cyclin A RNA is overexpressed in human breast cancer and breast cancer cell lines [ 20], higher expression in smaller and highly differentiated tumours, seemingly in contrast with the relation between cyclin A expression and higher cell proliferation. This may reflect the importance of this gene in the control of the normal cell cycle rather than in cell proliferation during tumour growth [ 38]. In addition, a study of cyclins in colorectal cancer showed the majority of tumours had reduced expression of cyclin A, diverging from the high cell proliferation rate [ 41].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of cyclin A in astrocytic tumours

Chakrabarty

Bridges

1998

Neuropathology Appl Neurobio

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Cyclins are important regulators of the cell cycle; there is increasing evidence that some cyclins are positively involved in carcinogenesis. Amplification and translocation of the cyclin genes and overexpression of their mRNAs and proteins have been observed in a variety of tumours. We studied cyclin A protein in astrocytic tumours by immunohistochemical analysis. Immunohistochemistry with microwave antigen retrieval was carried out on formalin fixed, paraffin embedded material from 15 glioblastomas (WHO grade IV), 10 anaplastic astrocytomas (WHO grade III), seven diffuse low grade astrocytomas (WHO grade II) and nine pilocytic astrocytomas (WHO grade I) using antibodies against cyclin A and a proliferation marker MIB1. Staining for these antibodies was seen mainly in the tumour cell nuclei; 66% of all cases showing staining for cyclin A and 95% of all cases staining for MIB1. Mean labelling indices (LI) for cyclin a were higher in glioblastoma (mean LI-6.7) and anaplastic astrocytoma (mean LI-5.9) than low grade diffuse astrocytoma (mean LI-1.7) and pilocytic astrocytoma (mean LI-0.12), although there was no clear cut off point between the various tumour types. A good correlation was seen between labelling indices of cyclin A and MIB1 (Pearson correlation coefficient r = 0.59, P < 0.0001). Cyclin A is variably expressed in astrocytic tumours, either reflecting increased tumour proliferation (cyclin A being an integral component of the cell cycle), an alteration of its gene, protein upregulation or regulation of apoptosis. The genetic basis of expression of cyclin A in astrocytic tumours remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of cyclin A in astrocytic tumours

Chakrabarty

Bridges

1998

Neuropathology Appl Neurobio

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Molecular Chemotherapy for Breast Cancer

Patterson

Harris

1999

Drugs & Aging

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Gene therapy for breast cancer initially involves local or systemic delivery. Local delivery may be intrapleural or via direct injection to lesions. However, systemic delivery remains the greatest challenge with targeting, although methods using antibodies or growth factor receptor ligands have been demonstrated in preclinical models. This review focuses on the next step of using tissue-specific promoters such as Muc-1, CEA, PSA, HER-2, Myc, L-plastin and secretory leukoproteinase inhibitor promoters. All of these have demonstrated differential upregulation in breast cancer and additional specificity may be obtained by using physiological stimuli that are more frequently expressed in cancers, such as glucose regulated promoters and hypoxia response elements or radiation inducible elements. Amongst the later are the EGR-1, p21 and tissue type plaminogen activator promoters. Potential therapy genes include the prodrug activation system 5-fluorocytosine and other analogues of antimetabolites, but all of these need gap junctions to transfer the phosphorylated metabolites. Other approaches involving more freely diffusible products include cyclophosphamide, ifosfamide and thymidine phosphorylase to activate 5-deoxy-5-fluoruridine to fluorouracil. The bystander effect is important both for cell killing and for immunological and antivascular effects. Breast cancer is one type of tumour where a major clinical research effort is underway using local delivery methods. For prodrug activation systems, the use of human enzymes is desirable to prevent an immunological response that would eventually eliminate cells producing the prodrug activation system. The use of alkylating agents has an advantage over antimetabolites in that they are cytotoxic to cycling and noncycling cells, and the cytotoxic products can diffuse across cell membranes without the need for gap junctions. They also have a much steeper dose response curve than antimetabolites.

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HER-2/neu, c-Myc and cyclin-A in human breast cancer

Cited by 2 publications

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Immunohistochemical analysis of cyclin A in astrocytic tumours

Immunohistochemical analysis of cyclin A in astrocytic tumours

Molecular Chemotherapy for Breast Cancer

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