In patients with aldosterone-producing adenomas either responsive or unresponsive to the renin-angiotensin system, no differences were detected using SSCP analysis in the coding region of the AT1 receptor gene in peripheral blood or tumour tissue.
These findings indicate that the ATM gene product plays an essential role in a diverse group of cellular processes, including meiosis, the normal growth of somatic tissues, immune development, and tumor suppression.
In addition, polymorphic subtypes of AT1 receptor do not seem to play a major role in the pathogenesis of these tumors, even though a tendency towards a higher frequency of the polymorphic base substitution at position 573 (T573-->C) in cortisol-producing tumors needs to be further evaluated.
Thus, our study demonstrates disruption of both ATM alleles by deletion or point mutation in T-PLL, suggesting that ATM functions as a tumor-suppressor gene in tumors of non-AT individuals.
The strong predisposition of AT patients to develop T-PLL and the high frequency of T-cell leukemias/lymphomas observed in atm-deficient mice, together with the known functions of the ATM protein, led us to evaluate the ATM gene as a potential tumor suppressor gene involved in T-PLL.
The ATM gene was shown to sustain frequent loss-of-function mutations in T-PLL tumor cells, consistent with functioning as a tumor suppressor gene in this leukemia.
ATM does seem to act as a classic tumor suppressor gene in T-prolymphocytic leukemia, and LOH at the ATM locus is a common event in some tumor types, suggesting a general role for ATM in cancer.
Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors.
For example, the gene ataxia telangiectasia mutated (ATM) has recently been shown to be a tumour suppressor gene in T-cell prolymphocytic leukaemia, and there is increasing evidence that individuals with one mutated ATM or Nijmegen breakage syndrome (NBS1) allele have an increased predisposition to cancer.
Recently, it has been shown that the ataxia-telangiectasia mutated (ATM) gene located at 11q23 is often deleted in T-PLL, suggesting a tumor suppressor role of the ATM gene on tumorigenesis of T-PLL.
A common assumption has been that the target for the LOH at 11q23.1 in breast carcinoma is the ATM gene, but the area studied has been too large, the density of markers too low, and the number of tumors studied has been too small to draw any firm conclusions.
Our study demonstrates somatic disruption of both alleles of the ATM gene by deletion or point mutation and thus its pathogenic role in sporadic B-cell lineage tumors.
In contrast to captopril challenge, PRA was suppressed by 30% in Case 1 and 42% in Case 2 in response to saline infusion, and was increased by 230% in Case 1 and 59% in Case 2 in response to furosemide-upright posture for 2 h. These results suggest that the short loop feedback inhibition of renin secretion by Ang II in JG cell tumor is closely related to AT1 receptor expression levels in the tumor tissue.
Defects are observed at all cell cycle checkpoints in A-T cells post-irradiation including the G1/S interface where ATM plays an important role in the activation of the tumour suppressor gene product p53.
The results indicate that a tumour suppressor gene (or genes) on chromosome 11q.23.1 may be involved in carcinogenesis of the cervix and the involvement of the ATM gene remains a possibility.