Synergistic cooperation between c-Myc and Bcl-2 in lymph node progression of T1 human breast carcinomas.
The overexpression of Bcl-2, an anti-apoptotic oncogene, identifies human T1 breast cancer patients who have an increased risk of lymph-node metastasis. We examined in these patients (n = 142) whether the c-Myc oncogene influences metastatic progression in conjunction or not with Bcl-2 expression and the loss of apoptosis in tumors. The association between Bcl-2 and lymph-node metastasis was only significant when c-Myc was concomitantly expressed (chi2 test, p = 0.008). Moreover, very large associations (pOR = 6.4) between c-Myc and lymph-node metastasis were observed among Bcl-2 positive tumors and tumors with loss of apoptosis (pOR = 8.4). In contrast, the metastatic advantage linked to Bcl-2 was decreased (pOR = 2) when c-Myc was not coexpressed. It is concluded that the synergism between Bcl-2 and c-Myc oncogenes may promote metastasis in breast tumors, linked to loss of apoptosis.
Sierra
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A
Dpt. Cancer i Metàstasis, Institut de Recerca Oncològica, Hospital Duran i Reynals, Ciutat Sanitaria i Universitaria de Bellvitge, Barcelona, Spain. asierra@iro.es
Castellsague
X
X
Escobedo
A
A
Moreno
A
A
Drudis
T
T
Fabra
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016015:Logistic Models; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008875:Middle Aged; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc