Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas.
Expression of the death-related proteins (DRPs) Bcl-2, Bax, Bcl-x and Bak that regulate cell survival and death was examined using immuno-histochemical methods in a group of 142 T1 (<2 cm) ductal breast carcinomas. Immunostaining results were correlated with loss of apoptosis and clinicopathological parameters such as histological grade (HG) and lymph node involvement. Expression of anti-apoptotic proteins Bcl-2 and Bcl-x was found in 57.0% and 62.75% of tumors, respectively. Bcl-2 expression, but not Bcl-x expression, was related to loss of apoptosis. Expression of the apoptotic proteins Bax and Bak was present in 58% of Bcl-2-negative tumors and associated significantly with an increase in apoptosis. Expression of these DRPs was associated significantly with the HG of the tumors: Bcl-2 and Bak expression was predominant in HG I/II tumors, whereas expression of Bcl-xL and Bax was commonly observed in HG III tumors, as occurs for p53 over-expression. Our results suggest that the loss or gain of apoptosis is regulated tightly in T1 breast carcinomas through the expression of different effectors along with tumor cell differentiation.
Sierra
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Department of Càncer i Metàstasis, Institut de Recerca Oncològica, Ciutat Sanitària i Universitària de Bellvitge, Barcelona, Spain. asierra@iro.es
Castellsagué
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X
Coll
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T
Mañas
S
S
Escobedo
A
A
Moreno
A
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Fabra
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A
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology*; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein