Dephosphorylation of cancer protein by tyrosine phosphatases in response to analogs of luteinizing hormone-releasing hormone and somatostatin.

Protein phosphorylation/dephosphorylation of tyrosine residues is an important regulatory mechanism in cell growth and differentiation. Previously it has been reported that RC-160, an octapeptide analog of somatostatin, and [D-Trp6]LHRH, an agonist of luteinizing hormone-releasing hormone (LHRH), stimulate receptor-mediated activity of tyrosine phosphatases (PTP) and reverse growth promotion of the tyrosine kinase (PTK) class of oncogenes in tumor cells. The effect of RC-160 and [D-Trp6]LHRH on protein phosphorylation was further examined in surgical specimens of human carcinomas.

EGF mediates multiple signals: dependence on the conditions.

Epidermal growth factor (EGF) has been reported to both increase and decrease proliferation and apoptosis. In KB cells, EGF-induced alteration in proliferation and apoptosis are concentration and time dependent. High concentrations of EGF (10(-7) and 10(-8) M) stimulated proliferation and inhibited apoptosis at 24 h, with apoptosis increasing with prolonged exposure.

Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro.

The conjugation of doxorubicin with [D-Lys6] Luteinizing Hormone-Releasing Hormone (LH-RH), yields AN-152, a cytotoxic analog that can be targeted to tumor cells expressing LH-RH receptors. This conjugate is more potent against LH-RH receptor positive cancer cells and has less peripheral toxicity than free doxorubicin. The proliferation of MCF-7 human breast cancer cells in vitro is inhibited by AN-152 and this effect can be augmented by the up-regulation of LH-RH receptor expression through stimulation of tyrosine phosphorylation with epidermal growth factor (EGF).

A conjugate of doxorubicin and an analog of Luteinizing Hormone-Releasing Hormone shows increased efficacy against oral and laryngeal cancers.

A doxorubicin and [D-Lys(6)]Luteinizing Hormone-Releasing Hormone (LH-RH) conjugate, AN-152, was designed to target LH-RH receptor positive cells. AN-152 is more potent against a specific group of cancers than doxorubicin and has less peripheral toxicity. This therapy is potentially efficacious against many other types of malignancies.

Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells.

The purpose of this study was to investigate the effects of a potent LHRH agonist, [D-Trp(6)]LHRH on the basal and EGF-induced cell proliferation and the metastasis-associated properties in A431 human epidermoid carcinoma. [D-Trp(6)]LHRH time-dependently inhibited the basal and EGF-stimulated growth of A431 cancer cells. It is assumed that phosphorylation/dephosphorylation of cellular proteins is highly related to cell growth.