Inverse effects of 20K and 22K human growth hormones on the growth of T‐47D human breast cancer cells in culture and in nude mice

Fujikawa, Takahiko; Kaneko, Hiroshi; Hibasami, Hiroshige; Sakaguchi, Kesami; Alam, Khorshed S. M.; Tanaka, Minoru; Nakashima, Kenichiro

doi:10.1080/15216549800204252

Cited by 3 publications

(1 citation statement)

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“…We also tested JAK2 tyrosine phosphorylation level in T-47D and obtained similar result (data not shown). Moreover, Fujikawa et al have recently reported that 20K-hGH suppressed the T-47D tumor growth, whereas 22K-hGH promoted it in estradiol-treated nude mice (48). These evidence suggest that the mitogenic effect of 20K-hGH on human breast cancer cells could be weaker as compared with that of 22K-hGH.…”

Section: Discussionmentioning

confidence: 95%

The 20-Kilodalton (kDa) Human Growth Hormone (hGH) Differs from the 22-kDa hGH in the Effect on the Human Prolactin Receptor

et al. 1999

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Previously we have demonstrated that 20-kDa human GH (20K-hGH) is a full agonist for hGH receptor (hGHR) even though its complex formation with hGHR and hGH-binding protein differs from that of 22-kDa human GH (22K-hGH). In this study, we focused on the effect of 20K-hGH on human PRL receptor (hPRLR). To elucidate the effects of 20K-hGH on hPRLR and compare them with those of 22K-hGH, we prepared two cells stably expressing full-length hPRLR, Ba/F3-hPRLR and CHO-hPRLR. In the proliferation of Ba/F3-hPRLR cells, which can grow in a dose-response to lactogenic hormones, both 20K- and 22K-hGH exhibited bell-shaped curves in the absence of exogenous zinc ion (Zn2+); however, the curve of 20K-hGH was shifted to a 10-fold higher concentration than that of 22K-hGH in view of EC50 value (the EC50 of 20K- and 22K-hGH were 15 nM and 1.5 nM, respectively). Addition of Zn2+ up to 25 microM increased the activities of both 20K- and 22K-hGH; however, the enhancement by Zn2+ was greater in 20K-hGH than in 22K-hGH, thereby the activities of both hGH isoforms reached the same level at 25 microM Zn2+. Nevertheless, in the presence of 0.25-1 microM free Zn2+, which is equal in human serum, the activity of 20K-hGH was still lower than that of 22K-hGH. The modest effect of 20K-hGH on activating hPRLR in the absence of Zn2+ was confirmed in the rat serine protease inhibitor 2.1 (Spi2.1) gene promoter activation and JAK2/Stat5 tyrosine phosphorylation in CHO-hPRLR. In addition, in human breast cancer cell T-47D, 20K-hGH was proved to stimulate Stat5 tyrosine phosphorylation to much lower degree than 22K-hGH via not hGHR but hPRLR. Taken together, our data suggest that 20K-hGH may be a weaker agonist for hPRLR than 22K-hGH in the human body; therefore 20K-hGH may alleviate the hPRLR-mediated side-effects such as breast cancer when administered to human body.

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Section: Discussionmentioning

confidence: 95%

The 20-Kilodalton (kDa) Human Growth Hormone (hGH) Differs from the 22-kDa hGH in the Effect on the Human Prolactin Receptor

et al. 1999

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Differential Secretion of Chicken Growth Hormone Variants After Growth Hormone-Releasing Hormone Stimulation In Vitro

Martínez-Coria

López-Rosales

Carranza

et al. 2002

ENDO

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Variants of growth hormone (GH) are present in most vertebrates. Chicken GH (cGH) undergoes posttranslational modifications that contribute to its structural diversity. Although the 22-kDa form of GH is the most abundant, some other variants have discrete bioactivities that may not be shared by others. The proportion of cGH variants changes during ontogeny, suggesting that they are regulated differentially. The effect of growth hormone-releasing hormone (GHRH) on the release of cGH variants was studied in both pituitary gland and primary cell cultures, employing sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, and densitometry. GHRH (2 nM, 2 h) stimulated the secretion of most of the size variants of cGH although the amplitude of increase was not equal for each one. A differential effect on the secretion of GH size variants, particularly on the 22- (monomer) and 26-kDa (putatively glycosylated) cGH isoforms was found in both systems. In the whole pituitary culture, the proportion of the 26-kDa immunoreactive cGH increased 35% while the 22 kDa decreased 31% after GHRH treatment in comparison with the controls. In the primary cell culture system, the proportion of the glycosylated variant increased 43% whereas the monomer and the dimer decreased 22.26 and 29%, respectively, after GHRH stimulation. Activators of intracellular signals such as 1 mM 8-bromo-cAMP and 1 microM phorbol myristate acetate had a similar effect to that obtained with GHRH. The data support the hypothesis that GH variants may be under differential control and that GHRH promotes the release of a glycosylated cGH variant that has an extended half-life in circulation.

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Structure and Properties of Members of the hGH Family

Lewis¹,

Sinha²,

Lewis

2000

Endocr J

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Abstract.This review will summarize the properties of five variant forms of human growth hormone: a disulfide dimer, a glycosylated form, 20 kD-hGH, and two peptides made up of portions of 22 kD-hGH.The two pituitary peptides (hGH1_43 and hGH44_191) have, respectively, insulin-potentiating and anti-insulin properties. Both have been detected in serum. The shorter peptide may prove to be useful in decreasing the amount of exogenous insulin required by diabetics. The larger, strongly anti-insulin peptide, may be involved in diabetic retinopathy.We believe that this peptide is the long sought after diabetogenic substance of the pituitary gland.

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Inverse effects of 20K and 22K human growth hormones on the growth of T‐47D human breast cancer cells in culture and in nude mice

Cited by 3 publications

References 5 publications

The 20-Kilodalton (kDa) Human Growth Hormone (hGH) Differs from the 22-kDa hGH in the Effect on the Human Prolactin Receptor

The 20-Kilodalton (kDa) Human Growth Hormone (hGH) Differs from the 22-kDa hGH in the Effect on the Human Prolactin Receptor

Differential Secretion of Chicken Growth Hormone Variants After Growth Hormone-Releasing Hormone Stimulation In Vitro

Structure and Properties of Members of the hGH Family

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