# TRANSPORT-REGULATED CALCIUM METABOLISM IN TUMOR CELLS

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 1987 · $143,210

## Abstract

The long-term objective is to identify the alterations of Ca2+ homeostasis
in hepatoma cells and characterize the biochemical basis for these
alterations.  The approach to this problem is based on the hypothesis that
the regulation of intracellular Ca2+ and (or) the metabolic sensitivity to
Ca2+ in tumor cells is modified so that cell survival and proliferation are
promoted even under adverse environmental conditions.  The specific aims of
this study are to:  1. Accurately compare the cytosolic free Ca2+
concentration of rat hepatoma cells and rat hepatocytes under normal and
metabolically-stressful conditions; 2. Compare the influence of
extramitochondrial or cytosolic free Ca2+ on the activity of Ca2+-
sensitive dehydrogenases and the TCA cycle in mitochondria from normal
liver and hepatoma cells; 3. Test the possibility that abnormally high
levels of membrane cholesterol are responsible for the abnormal Ca2+
buffering properties of hepatoma mitochondria; 4. Further characterize the
difference in the response of rat liver and hepatoma microsomes to release
of Ca2+ induced by inositol trisphosphate; 5. Compare the effects of
transient elevation of intracellular Ca2+ and depletion of ATP on the
respiratory and Ca2+-buffering characteristics of mitochondria and the Ca2+
transport activities of other Ca2+-sequestering organelles.  The methods of
approach will include the use of digitonin cell permeabilization,
fluorescent Ca2+ indicators, O2 and Ca2+ electrode measurements, dual beam
and dual wavelength spectrophotometry, steady-state measurements of 14CO2
ratios using metabolites labeled at different carbons, and TLC-flame
ionization determinations of membrane phospholipids.  The significance of
this work is that:  a. It will help explain how tumor cells are adapted for
survival in harsh environments; b. It will describe the relationships
between Ca2+ homeostasis and energy metabolism in tumor cells; c. It
relates to recent evidence that Ca2+ homeostasis is linked to the activity
of oncogene products via turnover of phosphatidylinositol; d. It may
ultimately lead to improved modes of cancer chemotherapy based on
manipulations of cellular Ca2+ metabolism.

## Key facts

- **NIH application ID:** 3170830
- **Project number:** 5R01CA032946-05
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **SAM.gov UEI:** ECR5E2LU5BL6
- **Principal Investigator:** GARY M FISKUM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $143,210
- **Award type:** 5
- **Project period:** 1983-07-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170830

## Citation

> US National Institutes of Health, RePORTER application 3170830, TRANSPORT-REGULATED CALCIUM METABOLISM IN TUMOR CELLS (5R01CA032946-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170830. Licensed CC0.

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