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Morphoproteomic and molecular concomitants of an overexpressed and activated mTOR pathway in renal cell carcinomas

Fan Lin1, Ping L Zhang, Ximing J Yang

  • 1Department of Pathology, University of Texas Houston Medical School, 6431 Fannin Street, Room 2.286, Houston, TX 77030, USA.

Annals of Clinical and Laboratory Science
|September 5, 2006
PubMed

Insights

The Akt-mammalian target of rapamycin (mTOR)-p70S6K pathway is commonly overexpressed and activated in renal cell carcinoma (RCC). This finding supports targeted therapies using rapamycin analogues for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The mammalian target of rapamycin (mTOR) pathway regulates cell proliferation and is a key mediator in various cancers.
  • CCI-779 (temsirolimus), an mTOR inhibitor, is under investigation for solid cancer treatment.
  • Understanding the Akt-mTOR-p70S6K pathway in renal cell carcinoma (RCC) is crucial for developing targeted therapies.

Purpose of the Study:

  • To evaluate the expression and activation of the Akt-mTOR-p70S6K pathway in RCC.
  • To determine if this pathway's activity in RCC supports the use of rapamycin or similar drugs for treatment.

Main Methods:

  • Immunohistochemistry was used to analyze phosphorylated Akt (p-Akt), p-mTOR, and p-p70S6K in 128 primary RCCs, 22 metastatic RCCs, and 24 normal kidneys (NK).
  • Western blotting was performed on 3 clear cell RCC (CRCC) cases and corresponding normal kidney tissues.
  • Scoring for immunostaining included location, distribution, and intensity, with NK serving as a baseline.

Main Results:

  • Expression of p-Akt, p-mTOR, and p-p70S6K was detected in nearly all RCC samples and normal kidneys.
  • Significantly higher levels of p-Akt, p-mTOR, and p-p70S6K expression were observed in RCC compared to NK (p <0.05).
  • Western blotting confirmed higher expression of these phosphorylated proteins in RCC tissues.

Conclusions:

  • Correlative overexpression and activation of p-Akt, p-mTOR, and p-p70S6K are common in RCC.
  • These findings provide a strong rationale for targeted therapy in RCC.
  • Combinatorial therapeutic approaches involving rapamycin-like agents and other small molecule inhibitors are proposed for future RCC clinical trials.

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