Apoptosis and expression of Bcl-2, Bcl-XL, and Bax in renal cell carcinomas.
There are at present disparate published results with regard to the relevance of the Bcl-2 gene family, levels of apoptosis, and cell proliferation in the development and progression of renal cell carcinoma (RCC). The present study analyses the inter-relationship between the expression of representatives of the anti-apoptotic (Bcl-2, Bcl-XL) or pro-apoptotic (Bax) Bcl-2 proteins, incidence of apoptosis, and mitosis in a selected small group of 22 graded RCCs that had paired normal renal tissue, or non-neoplastic tissue in the renal biopsy specimen. The cases were chosen to determine the feasibility of measuring these parameters as potential surrogate markers of progression or treatment failure of the cancers. The results showed that in approximately 50% of the RCCs, where Bcl-2 and/or Bcl-XL expression was high, apoptosis was not detected, and when expression of these proteins was low or not found, increased levels of apoptosis were seen. In most of the remaining 50% of samples, high levels of Bcl-XL but not Bcl-2 were negatively correlated with low levels of apoptosis (Bcl-XL: r = -0.437, P = 0.07 and Bcl-2: r = +0.560, P = 0.02). For the same group of samples, high Bax expression was found in association with apoptosis (r = +0.578, P = 0.02). A novel finding was an association between low expression of Bcl-2 and/or Bcl-XL in normal tissue and the level of expression of these proteins in the RCCs, an intrinsic variation that may be an individual patient factor. The results indicate that, in RCCs with increased expression of Bcl-2 and/or Bcl-XL, levels of apoptosis are minimal and these combined factors may assist in progression of the cancers and resistance to treatments.
Gobé
Glenda
G
Department of Pathology, Mayne Medical School, University of Queensland, Herston Road, Herston, Brisbane 4006, Australia. g.gobe@mailbox.uq.edu.au
Rubin
Mark
M
Williams
Gail
G
Sawczuk
Ihor
I
Buttyan
Ralph
R
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein